The clinical demand and supply of blood in India: A National level estimation study.

BACKGROUND: Estimating the clinical demand for blood and components arising in a health facility is crucial to ensure timely availability of blood. This study aims to estimate disease-specific clinical demand, supply and utilization of whole blood and components in India.
METHODS: We conducted a national level cross-sectional study in five randomly selected states from five regions of the country. We included 251 public and private facilities representing primary, secondary and tertiary care facilities. We collected annual disease-specific demand, supply and utilization of blood and components using a structured tool. We estimated the national demand by extrapolating the study data (demand and beds) to the total number of estimated beds in the country.
FINDINGS: According to the study, the total clinical demand of 251 health facilities with 51,562 beds was 474,627 whole blood units. Based on this, the clinical demand for India was estimated at 14·6 million whole blood units (95 CI: 14·59-14·62), an equivalent of 36·3 donations per 1,000 eligible populations, which will address whole blood and component requirement. The medicine specialty accounted for 6·0 million units (41·2%), followed by surgery 4·1 million (27·9%), obstetrics and gynecology 3·3 million (22·4%) and pediatrics 1·2 million (8·5%) units. The supply was 93% which is equivalent to 33·8 donations against the demand.
CONCLUSION: The study indicated a demand and supply gap of 2.5 donations per 1,000 eligible persons which is around one million units. The gap emphasises the need for sustained and concerted efforts from all stakeholders and for increasing the awareness about repeat voluntary non-remunerated blood donation (VNRBD); optimizing the availability of blood components through efficient blood component separation units; promoting modern principles of patient blood management and strengthening capacities of human resources in the blood transfusion system in India.

Introduction

Blood transfusion permits increasingly complex medical and surgical interventions to significantly improve the life expectancy and quality of life of patients [1]. The timely availability of safe blood is essential to address the clinical demand that arises in health care facilities to ensure appropriate treatment and minimise preventable mortality.

Clinical demand is the total number of units of whole blood and components required to meet all blood transfusions for emergencies and elective procedures at health facilities over a defined period. The current supply is the actual supply to healthcare facilities against the demand, and utilization is the actual utilization of the supplied blood by the healthcare facilities over a defined period [2]. Apart from the social, economic, geographical, and cultural factors, clinical demand is dependent on healthcare providers’ training, behavior and blood ordering practice within the health system capacity [3]. Ideally, a blood transfusion system should be capable of addressing 100% of clinical demand arising in healthcare facilities, within its catchment area. Yet, in many developing and under-developed countries, there is a widespread shortfall between demand and supply of blood due to several barriers. The major factors are increasing requirement for blood and blood products, poor implementation of voluntary donation and blood safety programs in countries, inadequate voluntary non-remunerated blood donation (VNRBD), suboptimal component separation, inadequate infrastructure, equipment and trained human resources, inappropriate use of blood and blood components, poor quality management systems, poor supply chain management systems, lack of cold chain, wastages and expiry of blood [1, 4, 5].

The blood transfusion service in India is fragmented with a network of 2,760 blood banks owned by the public, private and not-for-profit sectors, collecting around 12 million units in a year. Most (77%) blood banks were attached to hospitals and 22% were stand-alone. Around 51% had a component separation facility, separating 53% of the total annual collection in the country [6]. Despite the significant increase in the availability and use of components, whole blood is still requested and transfused substantially in clinical settings in India. As the majority of the health care facilities do not have blood banks on their premises, they are dependent on nearby blood banks or blood storage centres as available. Moreover, the proportion of voluntary blood donation is still around 80% and the remaining is depending on replacement donation by families or professionals in the guise of replacement donors. The National Blood Transfusion Council (NBTC) has regulated the cost of blood, both at public and private facilities. However, timely access to safe blood is still a challenge in many parts of the country which requires an efficient blood transfusion system. A comprehensive estimation of clinical demand, supply and utilization is critical to inform evidence-based blood donation and safety programs and strategies towards achieving universal access to blood. Challenged with a large population of approximately 1.4 billion, this study aims to estimate disease-specific clinical demand, supply and utilization of whole blood and blood components in India.

Materials and methods

Study and sampling design

We conducted a pilot study in Karnataka state, which was not included in the main study, to evaluate the feasibility of conducting the study, test the research protocols, data collection tools, sampling strategies, and estimate a statistically significant sample size for the study.

This study was a national level cross-sectional study conducted in five randomly selected states, one state each from five regions of the country, that are north, east, west, south and northeast (Fig 1). We randomly selected the required number of facilities from the list of primary, secondary and tertiary health care facilities representing the public and private sector, from the state specific list of health care facilities. We provisionally estimated the mean demand per bed as 9·6 (Standard deviation (SD: 6) units per annum through a pilot study. We had three strata- primary, secondary and tertiary care facilities. To estimate the demand of 9·6 (SD:6) units per bed with a precision of 0.1 units with 95% Confidence Interval (CI), we needed to study 13,830 units per stratum (primary, secondary and tertiary) which was rounded off to 15,000 units, totalling to 45,000 units of blood. Accounting for a design effect of two, we needed to study 90,000 units of blood per region, for which 9,000 beds were to be studied. We followed the proportional allocation method to allocate the samples to the strata. We considered 10%, 25% and 65% of primary, secondary and tertiary care beds respectively to transfuse blood, based on consensus among experts through four Delphi exercises conducted among 59 health care providers from across the country. We considered the average number of beds in primary, secondary and tertiary care facilities at 35, 120 and 1,000 and the presence of private and public facilities in India at the ratio of 60:40 [7]. Based on these considerations and to ensure 9,000 beds in each region, we decided to study 50 facilities from each state, of which 29 and 21 facilities were from private (58%) and public (42%) respectively. In total, we included 251 health care facilities in our study (Fig 2).

Fig 1

Study implementation region and states.

*States—Uttar Pradesh, West Bengal, Maharashtra, Tamil Nadu and Assam.

Fig 2

Sampling strategy.

The sampling frame consists of the list of facilities from the selected states from each region. From the public health care system, we included Community Health Centers (CHCs) as primary; sub-divisional (SDH) and district hospitals (DH) as secondary and medical colleges (MC) as tertiary care hospitals. In the private sector, we included facilities providing basic medical, surgical, Obstetrics & Gynecology (O&G) and pediatrics with less than 50 beds as primary facilities providing basic and specialty services with more than 50 beds as secondary, and facilities providing basic, specialty and super specialty services including medical colleges with more than 200 beds as tertiary facilities. We collected the lists of public and private health facilities from multiple sources and triangulated them to arrive at a state-wise list.

Data collection

We collected annual disease-specific demand, supply and utilization of blood and components from the participating health care facilities using a structured data collection form. The data included administrative details such as location, type of facility (public/private), level of care, number of beds, number of outpatients, admissions, bed occupancy rate, the average length of stay, and number of staff. The transfusion-related details included the number of patients with a disease or condition, number of patients requiring transfusion, number of units required per patient, percentage of blood supplied, utilized, discarded and/or returned to the blood bank under medicine, surgery, obstetrics and gynecology and pediatrics. We obtained these data primarily from the hospital and blood bank records manually. We conducted interviews with the heads of the administration and senior clinicians from these departments to validate the data and obtain additional information.

Data analysis and computation of clinical demand

The data were entered in REDCap (Research Electronic Data Capture), a secure web application for building and managing surveys [8, 9]. It was extracted as SPSS file and analysed using SPSS version 24 (IBM, Armonk, NY) [10]. As a first step, we computed disease-specific demand for each institution by summing the demand for whole blood and the demand for the highest component among red cells (RBC), plasma (FFP), platelets and cryoprecipitate because one unit of whole blood can provide one unit each of all components. Besides, it is based on 350 ml per donation which is generally practiced in India. Secondly, we computed the institution-wise demand for each department i.e., medical, surgical, obstetrics and gynecology and pediatrics, by calculating all the disease-specific demand of each department. Finally, we summed up the demand of all four departments to calculate the total demand for the institution. We calculated the actual supply and utilization using the percentage of supply and utilization provided by each institution.

We estimated the national demand by extrapolating the study data (number of beds and clinical demand in the study) to the total number of estimated beds in the country. As per the National Health Profile (2017) [11], India had 634,879 beds in the public sector, which is approximately 40% of the total beds. The remaining 60% was computed at 952,319 beds in the private sector. We used the sum of the public and private beds, which is 1,587,198 for extrapolation. The study included 51,562 beds, of which 40·3% were in the medical specialty followed by surgery (30%), obstetrics and gynecology (17·1%) and pediatrics (12·6%). Each of these four categories included general, specialties and sub-specialties beds. As demand for blood can occur only in occupied beds in a health care facility, we determined the bed occupancy rate (BOR) adjusted clinical demand per bed as well. After estimating the total demand in a health care facility, we adjusted for the actual bed occupancy. For this calculation, we used the total number of beds, bed occupancy rate to calculate the occupied beds and the total clinical demand in the health care facilities. Bootstrap method was used to get narrow confidence intervals for the estimation when the number of facilities per stratum was less than 50.

After estimating the total demand in a health care facility, it was adjusted for the actual bed occupancy. For this, we used the total number of beds, bed occupancy rate and the total clinical demand in the health care facilities.

Estimated number of the eligible donor population

To estimate the eligible donor population in the country, we considered the inclusion and exclusion criteria defined by the National Blood Transfusion Council (NBTC) and Drug and Cosmetics Act of India (1940), as amended up to 31st December 2016 [12]. We included the adult population between the age group of 18 to 65 years, which is 58·6% (745 million) of the total population in 2017 [13]. We excluded the pregnant women (estimated at 27 million) and people with anaemia, (adult male, 22·7% and adult female, 53%), hypertension (25·3%), diabetes (7·5%) and co-existence of any two or all the three conditions [7, 14]. We did not exclude the estimated 2·5 million cancer patients as anaemia coexists in the majority of cancer patients [15-17] Besides, we factored 5% for other temporary deferrals. Applying all these criteria, we conservatively estimated 402 million as eligible donor population in India.

Ethical approval

The study protocol was reviewed and approved by the Institutional Review Board (IRB) of Christian Medical College and Hospital, Vellore, India. We obtained approval from Technical Resource Group (TRG), Research and Development, National AIDS Control Organization (NACO), Ministry of Health and Family Welfare, Government of India and Associate Director for Science (ADS) and Associate Administrator for Science (ATSDR), the Centers for Disease Control and Prevention (CDC), Atlanta, USA.

For data collection from health care facilities, the National AIDS Control Organization (NACO), Ministry of Health and Family Welfare, Government of India, sent a letter of invitation to the medical head/administrator of all selected health care facilities to participate in the study. Following this, the study team approached the heads of the institutions over the phone to obtain their oral consent for the participation and convenient time for data collection. Before the data collection in the facilities, the study investigator obtained informed written consent from the heads of the institutions. For the Delphi exercises, we sent a letter of invite requesting the health care providers (technical experts) to participate in the study and their agreement to participate by a response mail was considered as their consent.

Results

The characteristics of healthcare facilities are mentioned in Table 1. The majority (76·5%) were in urban, around 57% were owned by the private sector, and two-thirds (67%) of the private sector were for-profit facilities. The average bed occupancy rates for primary, secondary and tertiary care facilities were 60·4% (SD: 25.9), 72·9% (SD: 24·7) and 83.9% (SD: 17·3) respectively. A third of the facilities (34%) had an attached blood bank.

Table 1

Details of healthcare facilities.

Components	Total	North Region	East Region	West Region	South Region	Northeast Region
Location	(n = 251) %	(n = 52) %	(n = 48) %	(n = 48) %	(n = 49) %	(n = 54) %
Rural	59 (23.5)	10 (19.2)	12 (25.0)	13 (27.1)	14 (28.6)	10 (18.5)
Urban	192 (76.5)	42 (80.8)	36 (75.0)	35 (72.9)	35 (71.4)	44 (81.5)
Ownership
Private	144 (57.4)	28 (53.8)	28 (58.3)	29 (60.4)	28 (57.1)	31 (57.4)
Public	107 (42.6)	24 (46.2)	20 (41.7)	19 (39.6)	21 (42.9)	23 (42.6)
Level of care
Primary	107 (42.6)	23 (44.2)	21 (43.8)	17 (35.4)	24 (49.0)	22 (40.7)
Secondary	113 (45.0)	23 (44.2)	21 (43.8)	24 (50.0)	19 (38.8)	26 (48.1)
Tertiary	31 (12.4)	6 (11.5)	6 (12.5)	7 (14.6)	6 (12.2)	6 (11.1)
Type of facilities (Public)
CHC	45 (42.1)	10 (41.7)	9 (45.0)	5 (26.3)	10 (47.6)	11 (47.8)
SDH/DH	47 (43.9)	11 (44.9)	8 (40.0)	11 (57.9)	8 (38.1)	9 (39.1)
MC	15 (14.0)	3 (12.5)	3 (15.0)	3 (15.8)	3 (14.3)	3 (13.0)
Type of facilities (Private)
Profit	96 (66.7)	14 (50.0)	23 (82.1)	18 (62.1)	20 (71.4)	21 (67.7)
Not for profit	48 (33.3)	14 (50.0)	5 (17.9)	11 (37.9)	8 (28.6)	10 (32.3)
Total number of beds
< = 50	111 (44.2)	23 (44.2)	22 (45.8)	20 (41.7)	24 (49.0)	22 (40.7)
51 Beds to 200	84 (33.5)	18 (34.6)	14 (29.2)	15 (31.3)	13 (26.5)	24 (44.4)
More than 200	56 (22.3)	11 (21.2)	12 (25.0)	13 (27.1)	12 (24.5)	8 (14.8)
Bed occupancy rate
Less than 25%	15 (6.0)	3 (5.8)	4 (8.3)	0	7 (14.3)	1 (1.9)
25% to 75%	132 (52.6)	29 (55.8)	23 (47.9)	27 (56.3)	22 (44.9)	31 (57.4)
More than 75%	104 (41.4)	20 (38.5	21 (43.8)	21 (43.8)	20 (40.8)	22 (40.7)
Attached blood bank
Yes	86 (34.3)	20 (38.5)	14 (29.2)	16 (33.3)	18 (36.7)	18 (33.3)
No	165 (65.7)	32 (61.5)	34 (70.8)	32 (66.7)	31 (63.3)	36 (66.7)

* Percentage in parenthesis.

Estimated national clinical demand

According to the study, the total clinical demand of 251 health facilities with 51,562 beds was 474,627 whole blood units. Based on this, the total clinical demand was estimated at 14·61 million units (95% CI: 14·59–14·62) of whole blood, which is equivalent to a requirement of 36·3 donations per 1,000 eligible persons, considering the existing blood transfusion practices and the amount of component separation in the facilities in India [18]. The estimated demand for medical specialty was 6·0 million units (41·2%), followed by surgery 4·1 million (27·9%), obstetrics and gynecology 3·3 million (22·4%) and pediatrics 1·2 million (8·5%) units (Table 2).

Table 2

Estimated national clinical demand.

	Study data n-251
Specialty	Number of beds	Clinical demand in whole blood units	Beds	Estimated national demand in whole blood units* (95% CI)
Medicine	20,779	195,434	639,641	6,015,910 (6,012,223–6,019, 597)
Surgery	15,469	132,370	476,159	4,074,654 (4,071,294–4,078,014)
Obstetrics & Gynaecology	8,817	106,312	271,411	3,272,529 (3,269,405–3,275,652)
Pediatrics	6,497	40,511	199,987	1,247,022 (1,244,929–1,249,115)
Total	51,562	474,627	1,587,198	14,610,116 (14,597,852–14,622,378)

*Estimated the national demand by extrapolating the study data (demand and beds) to the total number of estimated beds in the country.

Clinical demand per bed

The crude clinical demand per bed was 9·2 units (95% CI 7·5–9·5) and bed occupancy rate (BOR) adjusted clinical demand per bed was 11·2 (95% CI: 10·7–13·2) units per annum. It was found to be relatively lower in the northern region, rural areas, primary care facilities, public facilities, and in facilities without an attached blood bank (Table 3).

Table 3

BOR adjusted demand per bed in whole blood units.

Description	Demand per bed	BOR adjusted demand per bed	95% CI*
Region			Lower	Upper
North	8.2	10.3	7.9	12.5
East	9.3	11.3	10.5	15.9
West	9.7	12.1	9.5	14.5
South	8.6	10.7	9.9	15.8
North East	10.5	11.7	9.9	15.2
Location
Rural	6.5	9.1	6.4	11.8
Urban	9.5	11.4	11.2	14.0
Level of care
Primary	4.6	7.6	7.3	9.6
Secondary	9.4	12.3	10.9	13.8
Tertiary	9.6	10.9	8.8	12.4
Ownership
Public	9.5	10.3	7.7	10.6
Private	8.9	12.7	12.0	15.3
Availability of BBs
With blood bank	9.7	11.3	9.9	13.5
Without blood bank	6.9	10.5	7.5	11.6
Total	9.2	11.2	10.7	13.2

95% CI is based on bootstrap method using institution-level BOR adjusted demand per bed.

Major contributors of clinical demand

The diseases or conditions that recorded more than one percent of total specialty demand, medical, surgical, O&G and pediatrics are mentioned in Table 4.

Table 4

Major contributors of demand—medicine, surgery, obs & gyn and paediatrics (whole blood units).

Medicine	Demand	%	Surgery	Demand	%
Nutritional Anaemia	1,974,517	32.8	Orthopaedic Surgeries	1,015,636	24.9
End-stage renal disease (ESRD)	586,509	9.7	Abdominal surgeries	555,298	13.6
Gastro-Intestinal Bleed	346,463	5.8	Trauma	403,361	9.9
Dengue	334,027	5.6	Oncology surgeries	340,844	8.4
Chronic Liver Disorder	314,572	5.2	Head and Neck surgeries	275,802	6.8
Leukaemia	301,982	5	Adult cardiac surgeries	200,818	4.9
Oncological conditions	221,515	3.7	General surgeries	182,534	4.5
Others	199,751	3.3	Neurosurgical Procedures	154,031	3.8
Idiopathic Thrombocytopenic Purpura	169,984	2.8	Burns	141,718	3.5
Chronic Kidney Disease	141,202	2.3	Urology	100,409	2.5
Hemolytic anaemias	119,531	2	Thoracic surgeries	84,988	2.1
Malaria	113,528	1.9	Others	63,287	1.6
Myeloma & Lymphoma	100,199	1.7	Coronary artery bypass graft (CABG)	57,315	1.4
Autoimmune hemolytic anaemias	94,689	1.6	Road Traffic Accident (RTA)	52,852	1.3
Haemophilia	61,843	1	Pediatric cardiac surgeries	41,709	1
Rheumatic Heart Disease	60,242	1	Fracture	39,031	1
Disseminated Intravascular Coagulation	59,627	1
Sepsis	58,826	1
Others	756,903	12.6	Others	365,021	8.8
Sub-total	6,015,910	100	Sub-total	4,074,654	100
Obstetrics & Gynaecology	Demand	%	Pediatrics	Demand	%
Anaemia in pregnancy	1,120,428	34.2	Hemolytic anaemias–Thalassemia	294,363	23.6
Postpartum hemorrhage (PPH)–Caesarean, atonic, ret. Placenta, Traumatic Post-Partum Haemorrhage	484,119	14.8	Severe Nutritional Anaemia	175,885	14.1
Abnormal Uterine Bleeding	190,145	5.8	Leukemia	102,164	8.2
LSCS	153,052	4.7	Others	85,418	6.8
Abortions	148,496	4.5	Sepsis & Disseminated intravascular coagulation (DIC)	57,746	4.6
Hysterectomy–Abnormal uterine bleeding (AUB)AUB/ Prolapse/ Adenomysosis/ Endometriosis-Fibroids/ PID	123,654	3.8	Dengue	54,545	4.4
APH–Placenta praevia	96,104	2.9	Neonatal transfusions–Low Birth Weight	52,575	4.2
Ectopic pregnancies	89,516	2.7	Neonatal transfusions–Sepsis	44,325	3.6
Antenatal care (ANC)	89,177	2.7	Malaria	37,184	3
Fibroids–Myomectomy	88,900	2.7	Aplastic Anaemia	33,860	2.7
Placenta praevia—accrete/accreta	81,543	2.5	Gastrointestinal (GI) bleeding	31,890	2.6
Antepartum haemorrhage (APH)–Abruptio	74,894	2.3	Chronic renal disease	29,396	2.4
Carcinoma ovary	71,724	2.2	Neonatal transfusions–birth asphyxia/ trauma	26,472	2.1
Cancer cervix	62,150	1.9	Neonatal Jaundice	24,256	1.9
Postnatal care (PNC) with Anaemia	58,826	1.8	Thrombocytopenia	20,870	1.7
Hematology–Factor deficiency, All thrombocytopenia, Anticoagulation,	43,896	1.3	Haemophilia–severe	19,208	1.5
			Sickle Cell Anaemia	17,792	1.4
			Congenital Heart Disease	12,713	1
Others	2,95,905	9.2	Others	126,360	11.2
Sub-total	3,272,529	100	Sub-total	1,247,022	100

Medical specialty

Most of the demand was for nutritional anaemia (32·8%) which is equivalent to 1·97 million units followed by end-stage renal diseases (ESRD) (9·7%), gastrointestinal bleed (5·8%), chronic liver disorder (5·2%) and leukemia (5%). The demand for communicable diseases such as dengue and malaria were 0·45 million units, which is 7·5% of the medical demand.

Surgical specialty

The estimated demand for orthopedic surgeries was 25%, which is equivalent to around one million units. The demand for polytrauma and road traffic accidents was 0·46 million units which is around 11% of surgical demand. The demand for oncology surgery was 0·34 million units which is 8·4% of surgical demand.

Obstetrics & Gynecology specialty

A greater proportion of demand (34·2%) was for anaemia in pregnancy, which amounts to 1·1 million units for an estimated 27·7 million pregnant women in a year. Maternal and pregnancy-related complications such as ectopic pregnancy, antepartum hemorrhage–abruptio/placenta praevia, placenta accrete, and postpartum hemorrhage contributed around 25·2% which is around 0·8 million units. Whereas, gynecological cancers, accounted for around 4·1% (0·13 million units) of the gynecology demand.

Pediatric specialty

Hemolytic anaemia (predominantly thalassemia) is the leading contributor to the demand for pediatrics specialty (23·6%), followed by severe nutritional anaemia (14%) and leukemia (8·2%). Dengue and malaria contribute to 7·4% of clinical demand, which amounts to 91,729 units. Neonatal conditions such as very low birth weight (VLBW), sepsis, birth asphyxia/trauma and neonatal jaundice together account for 11·8% amounting to 0·15 million units.

National demand for blood components

The whole blood demand was estimated at 6·35 million units (95% CI: 6·34–6·36), red cell concentrates 6·61 million units (95% CI: 6·60–6·62), plasma 2·21 million units (95% CI: 2·20–2·22), platelets- 2·0 million units (95% CI: 1·99–2.02) and 0·22 million units (95% CI: 0·21–0·22) cryoprecipitate.

Current supply and utilization of whole blood and components

The supply against demand was estimated at 92·6% for whole blood, 91·7% for red cells, 86% for plasma, 77·5% for platelets, and 92·1% for cryoprecipitate. Similarly, the utilization against supply was reported at 98·7% for whole blood, 99·2%, 96·8% 97·6% and 94·6% for red cells, plasma, platelets and cryoprecipitate respectively (Table 5).

Table 5

Current demand, supply and utilization of whole blood and components (units).

Specialty	Whole Blood	Red cells	Plasma	Platelets	Cryo precipitate
Estimated national demand (in ‘thousands; 95% CI)	6,354 (6,350–6,358)	6,613 (6,609–6,617)	2,208 (2,206–2,211)	1,862 (1,859–1,864)	221 (220–222)
Total supply (in ‘thousands)	5,882 (5.879–5,886)	6,065 (6,062–6,069)	1,900 (1,898–1,903)	1,442 (1,440–1,445)	203 (203–204)
Total utilization (in ‘thousands)	5,807 (5,803–5,812)	6,016 (6,012–6,020)	1,838 (1,836–1,841)	1,407 (1,405–1,410)	192 (192–193)

Discussion

This national-level cross-sectional study is the first of its kind in India to estimate the gaps between clinical demand, supply, utilization. The estimated national clinical demand of 36·3 donations per 1,000 eligible population, is closer to the WHO’s suggested donation rate of one to three percent of a country’s population which would be sufficient to address the requirement [19].

The clinical demand primarily depends on the morbidity pattern, access to health services and capacity of health systems for service provision which vary between countries and within countries. Moreover, there has been a changing trend in the demand for blood over a period of time. A study in Tanzania estimated a demand of 6·2 blood donations per 1,000 persons after adjusting for irrational use and assuming 100% component separation which is significantly lower compared to our study [20]. In developed countries, the advent of modern technology, less invasive surgical procedures, pharmacological alternatives to transfusion, changing approach to the treatment of oncological conditions and effective patient blood management strategies have led to a reduction in demand and usage of blood. For instance, in the United States, there has been a decreasing trend of blood collection and transfusion that has fallen 25% since 2008 [21]. In Switzerland, a decrease of 18·6% of red cells demand has been predicted between 2013 and 2035 [22]. Germany indicated a 13.5% decrease in in-hospital transfusion demand from 2005 to 2015 [23].

In contrast, increasing demand is projected in underdeveloped and developing countries with improving access to health care. The Lancet Global Surgery Commission reports that there are about 143 million unmet surgical procedures in Low and Middle-income countries (LMIC) with a target to work towards achieving 5,000 procedures per 100,000 population, which may, in fact, increase the demand for blood [24].

The clinical demand per occupied bed is one of the critical indicators for planning transfusion services as demand is generated only from occupied beds in health care facilities. The demand per bed was higher in private facilities which could be due to the provision of highly specialized services such as dialysis and specialized surgeries that demand a higher volume of blood transfusions. Besides, the relative ease of availability of blood to the private health facilities, affordability of patients and possible non-adherence to strict guidelines could be the other contributing factors. The relatively higher BOR adjusted demand per bed in secondary care facilities could be due to the proximity, easy access, availability of all specialty services, and rational use of blood in tertiary care facilities which are mostly academic institutions.

Distribution of demand

According to our study, the demand for medical specialty was the highest, followed by surgery, obstetrics & gynecology and pediatrics respectively. Unlike the pattern in India, a study in Tanzania estimated a demand of 32·6% for medical specialty, 11.8% for surgery, 28·4% for obstetrics and gynecology and 26·8% for paediatrics [20].

In the medical specialty, nutritional anaemia (32%) which is an avoidable public health concern was the major contributor for the demand for blood followed by end-stage renal disease. Though theoretically, less than 7 g/dl require transfusion in anaemia, the actual clinical practice is not known clearly. In patients with co-existing morbidities that compromise cardiac function, and in places where critical care services are not available, the threshold may be higher. However, the study provides crucial evidence for the urgent need for anaemia screening and effective nutrition programs to prevent avoidable transfusion due to severe anaemia. The concerns linked to the increasing prevalence of non-communicable diseases in India are beginning to manifest with increasing numbers of patients with ESRD; many of these patients will experience anaemia and will require ongoing dialysis or renal transplantation, both of which are linked to increased demand for blood. Though early parenteral iron supplementations with erythropoietin (EPO) were found to be beneficial for the management of anaemia, especially in end-stage renal disease patients, it is not widely practiced as it is not feasible and affordable in India [25].

Among the seasonal febrile illnesses, dengue continues to be on the forefront, although experts agree that many of the platelet transfusions are unjustified, more often driven by caution and pressure from family members [26].

Around 28% of the total demand is for surgical specialties. The Lancet Commission on Global Surgery recommends at least 15 units per 1,000 persons per year which would be a significant volume of blood in India [24]. Besides, the increasing number of road traffic accidents implies that the demand for blood for trauma surgery will continue to be a significant contributor [27]. Increasing access to early diagnosis and treatment for oncological surgeries have also led to increased demand for blood which reflected a relatively higher demand of 0·34 million units [28-30].

In obstetrics and gynecology, the higher demand for anaemia during pregnancy, post-partum bleeding and abnormal uterine bleeding stress the importance of ensuring timely availability of blood to prevent avoidable maternal deaths. The higher demand for blood for caesarean section delivery (4·7%) reflects the increasing trend of surgical deliveries in the country. In pediatrics, the continuing burden of inherited hemolytic anaemia including thalassemia is one of the reasons for the high proportion of demand (23·6%) among children. Despite the substantial investment and efforts through national programs, the blood demand for severe nutritional anaemia among children indicates the need for revisiting the current strategies and programs related to anaemia.

Demand for blood components

The study provided evidence related to the specific demands for whole blood and components as well. It highlights the significant demand for whole blood in the country despite the continuous emphasis on rational use of blood through appropriate components. The possible reasons for the higher demand for whole blood could be the lack of knowledge and awareness among clinicians regarding component therapy, archaic clinical practices, lack of availability of blood component separation units, and sub-optimal component separation. Though the reported component separation rate was reported to be better (71%), the other reasons for the low demand for components need to be analyzed and addressed [18]. The demand for cryoprecipitate was found to be the lowest as it is used specifically for replacement of coagulation factor FVIII: C, von Willebrand antigen and fibrinogen in inherited and acquired conditions which are uncommon. Moreover, purified plasma-derived or recombinant clotting factor concentrates are easily accessible through national programs, which is an alternative for cryoprecipitate.

Supply against demand

Taking into consideration of the current supply against the demand for whole blood (92·6%) and red cells (91·7%), if the current supply in terms of whole blood donation is assumed to be around 93%, it will be equivalent to 33·8 donations against the estimated clinical demand of 36·3 donations per 1,000 eligible persons in India. The demand and supply gap of 2·5 donations per 1,000 persons, could be due to low voluntary blood donation, sub-optimal component production, injudicious demand and archaic practices. In 2013, the World Health Organization (WHO) reported significant variations in blood donation rates which were 32·1, 14·9, 7·8 and 4·6 per 1,000 persons per year in high, upper-middle, lower-middle and lower-income countries respectively. In the South-East Asia WHO region, the donation rates ranged from 1·8 to 30·8 (median 7·9) [31]. In 2006, the Sub-Saharan African countries collected less than half of their estimated minimum blood donation requirement [32] and Tanzania reported an unmet demand of 2·5% due to non-availability of blood [20]. There is a documented variation in the donation rates between regions and countries. However, it needs to be carefully interpreted as the computation of the eligible population who can donate may be different.

Utilization against supply

Though the reported utilization rate seems to be reasonable, the influence of supply-induced demand, irrational usage of blood due to societal pressure, defensive practice and other possible factors need to be studied further. The relatively lower utilization of plasma, platelets and cryoprecipitate could be due to the shorter shelf life and lack of temperature-controlled transportation system that could result in degradation of product [33]. This highlights the need for rational patient blood management practices and capacity building of clinicians and blood transfusion personnel in the country.

Limitations

We assumed that the weights will not have much impact on the estimates, since we had a high precision in the sample size estimation to account for the clustering effect. The study has limitations because it did not focus on analyzing clinician’s requests for each patient to determine the rationality of demand. Our study did not evaluate clinician ordering practices to determine if they were appropriate. The indications for blood transfusions and adherence to guidelines could vary between clinicians, health facilities and regions which could be potential limitations of the study.

The facility-wise supply and utilization data for each component were obtained as a percentage. Moreover, the declared official number of hospital beds may not be accurate in the facilities. The study did not factor in the possible disasters and epidemics that would generate demand which depends on their nature and severity.

Conclusion

Our study estimated a national demand of 14·6 million whole blood units, which translates to 36·3 donations per 1,000 eligible persons per year. The estimated BOR adjusted demand per bed was at 11·2 units per year. Although the gap between supply and demand is only 2·5 donations per 1,000 persons, which is around one million units, it requires sustained and concerted efforts from all stakeholders to address the gap.

The demand and supply gap emphasizes the need for increasing the awareness about repeat VNRBD; optimizing the availability of blood components through efficient blood component separation units; promoting modern principles of patient blood management and strengthening capacities of human resources in the blood transfusion system, to ensure universal access to blood and components in India.

13 Sep 2021

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Boris Bikbov

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2.Please note that Consent info is not provided, please provide your consent info.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

Reviewer #3: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: It’s my opinion that the manuscript is fairly good and well written. The information supplied is also relevant and timely. I have a few questions and some minor concerns. First, the authors should consider the use of a flow chart to describe the sampling strategy. The current approach appears to be long-winded, hence difficult to follow. Further, the authors should have incorporated more references on blood demand from other jurisdictions e.g. regional studies within India or Asia. Although these studies are rare, I’m sure a sufficient number or papers can be found in existing digital repositories. In addition, reference 17 and 22 are similar.

Reviewer #2: An important topic chosen by a group of authors from different fields, kudos to them. I have few observations which I feel you will be able to answer and further improve the article.

1. Introduction

a) Para 1 last line needs rephrasing

b) para 2 what programmes are being talked about

c) para 3 there is repetition and explanation of the same words, avoid semantics and reduce unnecessary words

2.The aim of the study in the abstract and main body is different, please explain.

3. The study used data from various different institutes, was the ethic clearance from each participating institute taken.

4. Table one says beds <30, 31-200 etc while text in methods says beds <50 as primary in pvt sector, please justify.

5. Table 4 needs to be made more reader friendly by reducing unnecessary rows.

6. Please explain 'Discussion " para 2 initial 4 lines

7. Discussion

a) Demand for blood components - has been written and appears out of context. a comment about the clinician's know;edge regarding components was not surveyed and should not be commented upon.

b) The discussion needs to be more specific and needs rewriting all over.

8. Please remove all the unnecessary comments from the conclusion which were not part of the aim & objectives. Please stick to the study per se and not the general comments

Thanks

Reviewer #3: Reviewer´s comments

Ms. No. PONE-D-21-22354

Ms. Title Demand and supply dichotomy of blood and components: A national level estimation study in India

Authors: Mamman J et al

The aim of this study, with authors representing health authorities in India, was to estimate clinical demand, supply and utilization of (whole?) blood and blood components, based on data from randomly selected facilities and then by extrapolating the study data, give estimates for the whole country.

General comments

The aim to estimate the supply and need of blood is ambitious and important, and it is a challenge, especially in a country like India, with a very large population and different levels of health care.

The effort and work are impressive, and it is an interesting descriptive report of the blood supply and usage, but the final estimations are based on many uncertain assumptions. It is not convincingly shown that the selected facilities are representative, the indications for blood transfusions varies and are in many parts not appropriate, according to guidelines in developed countries. The authors make reservations in the discussion and discuss the limitations of the study, but this could be further emphasized.

Specific comments

Title

I do not fully understand the title: Blood and components? The availability and use of blood components vs whole blood and the demand of different blood components are not analysed.

Something like “The blood supply in India-An estimation of available donors and demand and usage of blood transfusions on a national level”………?

Abstract

line 31 blood and components? Do you mean whole blood and blood components?

Line 35-36 are the regions, states and facilities all randomly selected? Not chosen as representative for different parts of the country and health care level?

Line 42-44 The study data, from where the national estimations are calculated should be presented.

Line 50-53 The conclusion should be more specific. What is the main message? Some of the findings discussed on page 15, line 282-306 and page 19 line 390-395?

Introduction

The introduction is informative, describing 2760 blood banks, public or private, often attached to hospitals, component preparation of 53% of the collected blood.

To interpret the data and results a short paragraph is requested of costs in the health care; is the health care free or paid for in public facilities? In private facilities? Are blood transfusions free or paid for? Are blood donors non-remunerated or compensated? Are relatives asked to donate?

Methods

Line 92-98. It would be nice with a map of India where you marked the regions and states and the selected facilities.

Line 98-100 how was the facilities randomly selected?

Line 98-99 define primary, secondary and tertiary health care facilities, with respect to blood transfusions/blood donations? It is partly explained later in line 108, “based on expert´s consensus”? Do you have a reference, documentation or is it an assumption?

Data collection

Line 133-134 How is the diagnosis and transfusion related information documented? Is it similarly documented in the different facilities?

Line 136-138 Please describe how you retrieved the data from the systems? Electronically or manually? Do all centers have electronic hospital and blood bank records?

Line 138 How was the data validated?

Data analysis and computation of clinical demand

Line 140 How was data entered in SPSS?

Line 157-158 Are the indications for whole blood and components different or is it a matter of tradition and availability?

Results

Line 219 Is nutritional anemia an appropriate indication for blood transfusion?

Discussion

The discussion includes many interesting aspects. Will the need of blood transfusions increase or decrease in India, referring to international trends? Are blood transfusions used on appropriate indications or is education primary needed?

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: Yes: DR SUSHIL CHAWLA

Reviewer #3: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

21 Feb 2022

A separate file indicating the reviewers comments and responses has been attached.

PONE-D-21-22354

Demand and supply dichotomy of blood and components: A National level estimation study in India

Response: The title has been changed as advised by the reviewers as below

The Clinical Demand and Supply Of Blood in India: A National Level Estimation Study

Editors Comments

1. Need to revision of the manuscript and rephrasing for clarity.

We have substantially revised and rephrased the manuscript for clarity

2. Preparation of a flow chart to describe the sampling strategy. Please describe not only general logic of sampling, but also provide the exact numbers of different facilities (private, public, tertiary, etc) considered during the sampling, and the exact numbers of finally selected facilities.

We have provided a flow with the number of facilities included in the study.

During the study, we were able to obtain the actual number of public health care facilities. (4,833 Community Health Centres (CHCs), 987 sub-divisional hospitals, 722 district hospitals and 381 medical colleges in the country). However, there was no single list private health care facilities in India. Therefore, we collected the state-wise list of private health care facilities from multiple sources such as Indian Medical Association of India, list of public/private hospitals empanelled under Rashtriya Swasthya Bima Yojana (RSBY), list of private hospitals empanelled under Central Government Health Scheme (CGHS) and other reliable sources. We triangulated the data from all sources to arrive at the tentative list of private facilities and obtained the samples from the list.

We have provided a flow chart for describing the sampling strategy.

3. Need to a clear distinction between blood and components.

In our study, we included both whole blood and its components. Despite the significant increase in the use of components, whole blood is still being requested and transfused in a significant proportion of health facilities in the country. Therefore, in our analysis, each unit of whole blood demand is equated to a single whole blood donation. Similarly, each unit of component demand is equated to a single whole blood donation. To avoid overestimation, we considered the component that recorded the highest demand among all components. It is due to the fact that one unit of whole blood can provide a minimum of one unit of components (Red cells, Plasma, platelets and cryo) each.

We have made the necessary changes in the manuscript for clarity.

4. More details on how is the diagnosis and transfusion related information have been documented.

The diagnosis and the transfusion-related information have been obtained from the Hospital records retrospectively for a period of 6 months. The details are provided in the data collection section of the manuscript.

Additionally, I suggest to:

1. Please provide the reference to the National Health Profile (2017).

Yes, we have provided the reference now.

2. The demand is one of the core concepts of the manuscript, and much more details on its calculation should be presented. The phrase "We computed the demand for whole blood or components by extrapolating the sum of whole blood or components demanded by each institution." is not clear. Please provide more details also on statistical methods (first of all about BOR adjustment).

We agree with the reviewer.

The phrase "We computed the demand for whole blood or components by extrapolating the sum of whole blood or components demanded by each institution." is not clear. We removed the phrase as the details have been given earlier in the paragraph.

As demand for blood can occur only in occupied beds of a health care facility, we determined the bed occupancy rate (BOR) adjusted clinical demand per bed. After estimating the total demand in a health care facility, it was adjusted for the actual bed occupancy. We used the total number of beds, bed occupancy rate and the total clinical demand in the health care facilities.

For example, if the total demand for a 100 bedded hospital is 1000 in a year. The demand per bed per annum is 1000/100 = 10. If the average bed occupancy rate is 80%, the beds used were 80. Therefore, the BOR adjusted clinical demand per bed is 1000/80 = 12.5 units per bed per annum.

3. Please provide in the footnote of all tables the definitions of abbreviations used.

Thanks and we corrected the errors and provided the abbreviations.

4. In the Table 2, please use the same digit capacity for the "Clinical demand in whole blood units" for the columns related to study data and national estimates.

Thanks for the comment. We have corrected

5. In the Table 3, please introduce a column with "demand per bed before adjustment" data.

Thanks. The additional columne has been provided.

6. The number of blood transfusions for the Nutritional Anemia is impressive. Could you please comment in the Discussion which haemoglobin level is the indication of blood transfusion for this population?

The details have been incorporated in the discussion section

7. The second most prevalent category requiring blood transfusion is patients with End-stage renal disease. Could you please comment in the Discussion about availability of erythropoetin and parenteral iron medications in India, as well as which haemoglobin level is the indication of blood transfusion in this particular disease? You provided separate estimates for "End-stage renal disease" and "Chronic Kidney Disease" - could you please comment on it?

Your comments have been addressed in the manuscript.

EPO is available in India but not easily afforded by most of the patients, with a year’s therapy running into several hundreds of thousands of Indian rupees (between 2000 – 5000 USD). The haemoglobin level targeted is above 10g/dL. However, immediate determinants include the availability of blood, and cost. In centres where renal transplant is carried out, constraint is exercised to avoid alloimmunisation for red cells antigens and HLA antigens and where possible leuko-reduced blood is transfused.

8. In the Table 3 the "Sepsis" and "Disseminated Intravascular Coagulation" are 2 separate categories for adults, but one merged category for paediatric care. Please could you explain why the same questionnaires applied have led to different categories?

On discussion with the experts in the domain (paediatrics and paediatric critical care), it was found that often it was difficult to make a clear-cut difference between the two conditions, especially in critical paediatric patients. Often, the delay in seeking appropriate care would mean the child was septic and progressing to DIC at admission in emergency services.

For all practice purposes, we clubbed Sepsis in DIC in paediatrics.

9. In the tables, please use "in thousands" instead of "(in ‘000)".

The tables have been corrected

10. It would be better to use "general medicine" instead of "medical specialty", where appropriate.

We prefer keeping this as “medical speciality” as it is going beyond general medicine (Internal Medicine) as we are considering all sub specialities under this term.

11. While only 30-40% of considered facilities have their own blood bank, could you please describe some details on how the blood or components are distributing from facilities with to those without blood bank? It would be also interesting to know more about blood donation in India - whether donors have some incentives, are there any cultural or religious patterns of blood donation, etc.

Thank you very much for your comment. We highlighted a few aspects in the background section.

12. Please indicate the volume for the whole blood and components used. Even if their volume per unit is standard, the clear definition is always a good choice.

It is based on 350 ml per single donation which is generally practised in India. We have mentioned it in the method section.

13. Please avoid abbreviations in the references where possible. Please control for the references completeness, for example "IIPS. National Family Health Survey-2017 (NFHS-4) New Delhi: International Institute for Population Sciences, Ministry of Health and Family Welfare, 2017" would be better to supply with ISBN or web-link.

We have addressed the issues

14. It is up to your choice, but it would be useful to share the questionnaire in the supplement, to give the opportunity to reproduce the study for other LMICs research groups.

We have included the tools as an attachment.

________________________________________

5. Reviewers comments to the Author.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1:

It’s my opinion that the manuscript is fairly good and well written. The information supplied is also relevant and timely. I have a few questions and some minor concerns. First, the authors should consider the use of a flow chart to describe the sampling strategy. The current approach appears to be long-winded, hence difficult to follow. Further, the authors should have incorporated more references on blood demand from other jurisdictions e.g. regional studies within India or Asia. Although these studies are rare, I’m sure a sufficient number or papers can be found in existing digital repositories. In addition, reference 17 and 22 are similar.

• We have given a flow chart to describe the sampling strategy

• As you rightly mentioned, there is a dearth of literature related this topic. We tried our best to use the available literature.

• Yes, reference 17 and 22 are similar. We have corrected it.

Reviewer #2:

An important topic chosen by a group of authors from different fields, kudos to them. I have few observations which I feel you will be able to answer and further improve the article.

1. Introduction

a. Para 1 last line needs rephrasing

Rephrased

b. para 2 what programmes are being talked about

Voluntary donation and blood safety programmes in countries. Rephrased.

c. Para 3 there is repetition and explanation of the same words, avoid semantics and reduce unnecessary word

Rephrased and added some more details based on editor’s comments

2. The aim of the study in the abstract and main body is different, please explain.

Rephrased and added some more details based on editor’s comments

3. The study used data from various different institutes, was the ethic clearance from each participating institute taken.

We have not obtained from ethic clearance from each participating institute though we obtained informed consent from all the participating institutes. Moreover, not all participating institution have ethics committee.

This study is led by the National AIDS Control Organization, Ministry of Health and Family Welfare, Government of India. We obtained clearance from the Ethics committee of the National AIDS Control Organization, Institutional Review Board of Christian Medical College and Hospital, Vellore, India. Besides, this proposal was cleared by the Technical Resource Group (TRG) of Research and Development, National AIDS Control Organization followed by the scientific committee approval from Centres for Disease Control and Prevention, Atlanta.

4. Table one says beds <30, 31-200 etc while text in methods says beds <50 as primary in pvt sector, please justify.

Yes, we agree. Both are different, we provided the bed details to categorise the type of facilities as primary, secondary and tertiary for this study.

While we provided the type of facilities in Table -1, we also provided a different category based number of beds as well. We have modified the categories now.

5. Table 4 needs to be made more reader friendly by reducing unnecessary rows.

There are only two empty rows. To have the sub-headings in the same row, we made it like that.

6. Please explain 'Discussion " para 2 initial 4 lines

Thanks for the comment. We understood the issues and we have modified the paragraph.

7. Discussion

a) Demand for blood components - has been written and appears out of context. a comment about the clinician's knowledge regarding components was not surveyed and should not be commented upon.

We intend to bring the substantial use of whole blood despite the continuous emphasis on rational use of blood through appropriate component use in India through the National programmes. We discussed the lack of clinician’s knowledge as one of the possible reasons for the extensive use of whole blood in the country. We rephrased the paragraph too.

b) The discussion needs to be more specific and needs rewriting all over.

We have rewritten/rephrased for better clarity.

8. Please remove all the unnecessary comments from the conclusion which were not part of the aim & objectives. Please stick to the study per se and not the general comments

We have revised the conclusion section

Reviewer #3:

The effort and work are impressive, and it is an interesting descriptive report of the blood supply and usage, but the final estimations are based on many uncertain assumptions. It is not convincingly shown that the selected facilities are representative, the indications for blood transfusions varies and are in many parts not appropriate, according to guidelines in developed countries. The authors make reservations in the discussion and discuss the limitations of the study, but this could be further emphasized.

The study is based on primary data collected from health facilities that transfuse blood and we extrapolated for the country based on the number of beds. Though we do not disagree with the reviewer’s comment about the representation of the study facilities, we would like to emphasise that we followed a sampling strategy that represented all the regions, the different levels of service provision (primary, secondary and tertiary facilities) and type of facilities (public and private) and geographies (rural and urban).

As suggested we have highlighted the issues in the limitation section.

Specific comments

Title

I do not fully understand the title: Blood and components? The availability and use of blood components vs whole blood and the demand of different blood components are not analysed.

Something like “The blood supply in India-An estimation of available donors and demand and usage of blood transfusions on a national level”………?

We have titled it as:

The clinical demand and supply of blood in India: A National level estimation study

Abstract

line 31 blood and components? Do you mean whole blood and blood components?

Yes, we have corrected

Line 35-36 are the regions, states and facilities all randomly selected? Not chosen as representative for different parts of the country and health care level?

We rephrased it and provided less information due to the word limit. The detailed sampling strategy is in the main text.

Line 42-44 The study data, from where the national estimations are calculated should be presented.

We have presented the study data in the abstract and the manuscript.

Line 50-53 The conclusion should be more specific. What is the main message? Some of the findings discussed on page 15, line 282-306 and page 19 line 390-395?

Revised

Introduction

The introduction is informative, describing 2760 blood banks, public or private, often attached to hospitals, component preparation of 53% of the collected blood.

To interpret the data and results a short paragraph is requested of costs in the health care; is the health care free or paid for in public facilities? In private facilities? Are blood transfusions free or paid for? Are blood donors non-remunerated or compensated? Are relatives asked to donate?

We have highlighted a few aspects in the introduction section.

Methods

Line 92-98. It would be nice with a map of India where you marked the regions and states and the selected facilities.

We have included a map marking the regions and selected states. However, marking the selection of facilities may be difficult with 251 facilities.

Line 98-100 how was the facilities randomly selected?

The required number of facilities for each strata was randomly selected from the state specific disaggregated list of health facilities. We rephrased the sentence for better clarity.

Line 98-99 define primary, secondary and tertiary health care facilities, with respect to blood transfusions/blood donations? It is partly explained later in line 108, “based on expert´s consensus”? Do you have a reference, documentation or is it an assumption?

As part of the blood estimation exercise, we conducted Delphi exercise among 50 health care providers from different parts of the country. The expert consensus was based on that. It is included in the manuscript.

Data collection

Line 133-134 How is the diagnosis and transfusion related information documented? Is it similarly documented in the different facilities?

These are from the hospital records and the diagnosis are similarly documented to a greater extent, since the Blood transfusion services is regulated and licensed. Doubtful information was verified with the clinicians of the respective health care facilities. The transfusion-related information such as the type of components and units were documented similarly.

Line 136-138 Please describe how you retrieved the data from the systems? Electronically or manually? Do all centers have electronic hospital and blood bank records?

We obtained these data primarily from the manual hospital and blood bank records as all hospitals in our sample maintained manual records

Line 138 How was the data validated?

The data from the records were checked again for correctness and completeness by another investigator. The doubtful information was verified with the support of the clinicians of the health care facilities.

Data analysis and computation of clinical demand

Line 140 How was data entered in SPSS?

The data were entered in REDCap application, converted and analysed using SPSS version 24 (IBM, Armonk, NY). We have mentioned it in the manuscript.

Line 157-158 Are the indications for whole blood and components different or is it a matter of tradition and availability?

It is primary based on availability of components and in some instances, the whole blood was due to non-availability of components and common practice.

Results

Line 219 Is nutritional anemia an appropriate indication for blood transfusion?

Yes, it is. This is as indicated in the patient records. It is common in India.

Discussion

The discussion includes many interesting aspects. Will the need of blood transfusions increase or decrease in India, referring to international trends? Are blood transfusions used on appropriate indications or is education primary needed?

The demand for blood transfusion indicates a decreasing trend due to increased knowledge and awareness and increasing adherence to principles of patient blood management, though it is difficult to arrive at a conclusion as our study is a cross-sectional one. Certainly, there is a need for education among health care provides to ensure rational and appropriate use of blood in India. This has been emphasised in the discussion and conclusion of the manuscript.

________________________________________

Submitted filename: Responses to reviewers comments_5Feb2022.docx

Click here for additional data file.

11 Mar 2022

The clinical demand and supply blood in India: A National level estimation study

PONE-D-21-22354R1

Dear Dr. Mammen,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Boris Bikbov

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #3: I find that that the authors have addressed the comments and objections appropriately. They have clarified the issues with inclusion of centers, indication for blood transfusions, calculations, etc. I think the manuscript gives interesting information of blood supply and demand in India, and the information may also be representative for other countries. I appreciate the added limitations of the study, and requirement of education and implementation of other treatment strategies in nutritional anemia.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #3: Yes: Agneta Wikman, Professor, Senior Consultant, Transfusion Medicin, Karolinska Institutet

28 Mar 2022

PONE-D-21-22354R1

The clinical demand and supply of blood in India: A National level estimation study

Dear Dr. Mammen:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Boris Bikbov

Academic Editor

PLOS ONE