Incidence of sickle cell disease patients with pulmonary embolism admitted to the intensive care unit in Bahrain.

OBJECTIVES: To describe the incidence of pulmonary embolism (PE) in sickle cell disease (SCD) patients admitted to the intensive care unit (ICU).
METHODS: A retrospective descriptive analysis was conducted with 124 SCD patients diagnosed with PE or suspected PE admitted to the ICU of Salmaniya Medical Complex, Manama, Bahrain between May 2017 and April 2018. A data collection form was used to obtain information on the history and demographics of PE patients.
RESULTS: A total of 124 patients diagnosed with SCD were admitted to the ICU during the study period. Male patients slightly outnumbered (n=75; 56.4%) female patients, and the average age was in the mid- thirties (mean=37.4 years). The main diagnosis leading to ICU admission was vaso-occlusive crisis. The average hemoglobin level was 8.6 mg/dl, hemoglobin S% was 55.8%, and the length of stay in the ICU was 5.3 days. A total of 5 patients were diagnosed with PE with an incidence rate of 3.8%. All PE patients were females, which resulted in a significant relationship between gender and the likelihood of developing PE. No statistical relationship existed between the likelihood of developing PE and patient age, hemoglobin, hemoglobin S%, length of stay in ICU, and mortality.
CONCLUSION: The demographic characteristics of the population included a male predominance, age in the mid-thirties, and vaso-occlusive crisis diagnosis upon admission to the ICU. The incidence of PE was significantly related to female gender. No significant relationship existed between the likelihood of developing PE and age, hemoglobin, hemoglobin S%, length of ICU stay, or mortality.

Sickle cell disease (SCD) is a group of inherited diseases that affect hemoglobin, which delivers oxygen to cells throughout the body. Patients with this disorder have atypical hemoglobin molecules called hemoglobin S (HbS) or sickle hemoglobin. Sickle cell disease is inherited in an autosomal recessive pattern.1 Vascular obstruction due to the distorted sickle shape of red blood cells (sickling) and endothelial adherence to erythrocytes can result in damage to different organs or systems.2 The most common complications associated with SCD include vaso-occlusive crisis (VOC), severe anaemia, infection, acute chest syndrome, thromboembolism, multiorgan failure with poor outcome and early mortality.[3-5]

Venous stasis, turbulent blood flow, and a hypercoagulable state often cause deep venous thrombosis (DVT) and pulmonary embolism (PE).6 Patients with SCD exhibit an elevated baseline level of coagulation and are at an increased risk for venous thrombosis and PE.[7,8] Factors associated with thrombosis and embolism include cancer, trauma, infection, obesity, and recent lower extremity orthopedic surgery.[6,9-11]

The prevalence of PE is higher for hospitalized SCD patients than for non-SCD patients and is likely under-diagnosed.[7,12] Treatment of PE can greatly reduce mortality.13 Sickle cell disease is much more common in certain ethnic groups and is considered one among the most prevalent genetic blood disease within the Gulf region, including Bahrain. In a study by Al-Arrayed et al,14 56198 blood tests of Bahraini individuals were analyzed over 6 years. Sickle cell disease prevalence was reported as 2.1%. The study described that the mild type of SCD among Bahrainis was predominant, but wide clinical variability was apparent.14

Although life expectancy of SCD patients has drastically improved, pulmonary complications attribute to a high death rate among young individuals.15 For instance, Alkhawaja et al,16 concluded that the death rate of SCD patients was 12.7% among 210 patients in the intensive care unit (ICU) of the Salmaniya Medical Complex (SMC), which is the largest and core government hospital in Bahrain. Comparing to non-SCD patients, PE incidence is higher in SCD patients, suggesting that PE may be under-diagnosed.12

Due to the lack of information about the incidence and demographic characteristics of SCD patients with PE and suspected PE admitted to the ICU in the SMC hospital in Bahrain, a retrospective descriptive analysis was performed in this study to help ICU staff identify SCD patients at highest risk of PE in the Kingdom of Bahrain.

Methods

The study was carried out at the ICU department with a 22 bed capacity in Salmaniya Medical Complex (SMC), Manama, Bahrain which is the largest tertiary teaching and the central government hospital in Manama, Bahrain.

All SCD patients (n=124) were admitted to the ICU with a diagnosis of PE or suspected PE during the period between May 2017 and April 2018. All patients with PE were diagnosed upon admission.

The study design was retrospective and descriptive. The inclusion criteria included all SCD patients admitted to the ICU during this period despite age, gender, comorbidities or number of admissions and the exclusion criteria was non-SCD patients with PE.

Data collection

The research team developed a data collection form. The study was authorized by the Secondary Health Care Research Sub Committee, SMC. Moreover, formal consent was obtained from patients prior to the completion of data forms. The form included the patient’s name, gender, age, admission diagnosis, hemoglobin (Hb) and hemoglobin S% (HbS%) on admission, ICU length of stay, comorbidities and computed tomography (CT) angiography findings. Patient’s data was collected from the registration book and the electronic I-Seha. Meticulous care was taken during the identification of data and data entry. Multiple measures were taken to ensure data accuracy.

Statistical analysis

The Statistical Package for Social Sciences, version 20 (IBM Corp, Armonk, NY, USA) was used to analyze the collected data. Descriptive and inferential statistics for demographic variables, illness-related variables and PE incidence were conducted. The variables relations were investigated with the proper statistical methods (t-test, ANOVA, Pearson correlation and Chi-square test).

Results

Information on patient’s gender and age is listed in . The sample consisted of 124 patients with a total of 133 admissions to the ICU. Male patients (n=75, 56.4%) slightly outnumbered their female counterparts (n=58, 43.6%). On average, the study participants were fairly young and in their mid-thirties (mean=37.4 years). Despite the mean age of males being 4 years older than that of females, the difference was not statistically significant.

Diagnosis

In addition to their principal diagnosis as SCD patients, the sample presented with approximately 20 different admitting diagnoses, as shown in . The predominant admitting diagnosis was VOC, as it was reported in 62.4% of the cases. This diagnosis was followed by gastrointestinal (GI) conditions (9.8%), gynecological conditions (7.5%), and acute chest syndrome and chest infection (4.5%). The rate of orthopedic conditions reported to be 3.8% and that of PE was 3.7%. The least common diagnosis was anemia (3%) and other conditions (2.2%). Some of the patients were admitted with more than one diagnosis.

Hemoglobin, HbS% on admission and length of stay in the ICU

The SCD subjects had an average hemoglobin of 8.6 mg/dl. Moderate variability among the subjects was reflected by a standard deviation of 2.2, as shown in .

The average HbS% was relatively high (mean=55.8%), with noticeable variation among the subjects, as evidenced by a high standard deviation (21.1).

The sample has an average length of stay (LOS) of 5.3 days. A very noticeable variation among the SCD subjects in this regard was reflected by a relatively large standard deviation of 6.4 days.

Incidence of pulmonary embolism

Among the 133 reviewed admissions of SCD patients to the ICU, only 5 patients were diagnosed with PE. This resulted in an incidence rate of approximately 3.8%.

Incidence of PE and gender

All the SCD patients diagnosed with PE were females (n=5), representing 8.6% of the total females in the sample (n=58). This finding suggests that there might be a relationship between the patient’s gender and his/her likelihood of developing PE. This possibility is further supported by the statistically significant results of the Chi-square test (X2=6.7, p=0.015) ().

Incidence of PE and age, Hb and HbS% on admission and LOS in the ICU

There was no relationship between the subjects’ ages and their chances of developing PE. Both groups (negative PE and positive PE) were very similar in age on average without statistically significant differences.

No relationship existed between the patient’s Hb on admission and his/her likelihood of developing PE. This finding was confirmed with a statistically nonsignificant t-test (t=0.62, p=0.511) since the difference between the mean Hb of patients with PE and that of their counterparts was not large enough.

No relationship existed between the patient’s HbS% on admission and his/her likelihood of developing PE. This finding was confirmed with a statistically nonsignificant t-test (t=0.01, p=0.991). The difference between the mean HbS% of patients with PE and that of their counterparts was not large enough.

No relationship existed between the patient’s LOS at the ICU and his/her likelihood of developing PE. This finding was confirmed with a statistically nonsignificant t-test (t=0.188, p=0.851) since the difference between the mean LOS of patients with PE and that of their counterparts was not large enough.

Discussion

Micro- and macrovasculature occlusion is the most important pathophysiological occurrence in SCD and explains most of its clinical manifestations.2 Sickle cell disease patients had significantly higher risk for venous thromboembolism, PE and DVT, comparing to non SCD adults.17 The age of 42 years for men and 48 years for women were the median age of death.4 Pulmonary embolism and thrombosis are usually caused by clotting disorders, decreased mobility, recent history of surgical procedure, obesity, cancer, deep venous thrombosis, pregnancy or post partum.[7-9,18,19] Risk factors for venous thromboembolism recurrence in SCD included lower extremity DVT as the incident event, pneumonia or acute chest syndrome.20

In SMC, the 22 adult beds in the ICU admit both medical and surgical cases, including trauma patients. Sickle cell disease with VOC was the principal reason for admission (n=83, 62.4%), accounting for more than two-thirds of cases. This high percentage is due to the possibility of rapid clinical status deterioration in some cases and poor outcome, which necessitates ICU care.[21,22] Gastroenterological complications related to SCD were found in 11 patients. Ten SCD patients with gynecological conditions were transferred to the ICU either with low Hb or post-labor for observation. Acute chest syndrome was present in 6 cases, and chest infection was present in another 6 cases. Five patients were admitted to our ICU with orthopaedic conditions related to SCD, and PE was found in another 5 patients. The least common diagnosis among SCD patients was anemia. Other conditions included pulmonary hypertension, acute tonsillitis and decompensated cardiomyopathy. In other studies, the primary reason of ICU admission was acute chest syndrome (ACS) with 55% in Bahrain, 69.9% in Oman, and 30.4% in the United Kingdom.[16,22,23] The reason was that some patients were shown to have more than one complaint and more than one organ involved, which may be related to the nature of SCD and the pathophysiological sickling process.

In the ICU, the level of Hb at the time of admission was 8.6 mg/dl. This finding was similar to those of other studies, with 8.6 mg/dl in survivors and 8.7 mg/dl in nonsurvivors in Bahrain; and, 8.3 mg/dl in survivors and 8.6 mg/dl in nonsurvivors in Oman.[16,23] At admission, the mean HbS was 55.8% with a standard deviation of 2.2. The Omani study revealed the mean HbS was 63% in survivors with a standard deviation of 21.5% and 54.5% in non-survivors with a standard deviation of 25.2.23

In this study, ICU LOS extended between 1 to 45 days, and the average stay was 5.3 days. Our findings were similar to those of earlier Bahraini and Omani studies.[16,23] While in New York, United States of America (USA), average hospital LOS was 15.35 days with average ICU LOS of 3.63 days of 141 adults SCD patients over a 6 year period.24 This result can be attributed to the nature and complexity of the disease and the need for intensive supportive measures. The other explanation could be the delay of transfer to the ICU.

Among SCD patients admitted to the ICU, 5 patients were diagnosed with PE. This resulted in an incidence rate of 3.8%. In California, USA, among 6237 SCD patients, 11.2% developed incident venous thromboemblosim: 51.6% had PE (±DVT), 25.7% had lower extremity DVT and 22.7% had upper extremity DVT.25 In Pennsylvania, USA, from 2001-2006, PE incidence was 50-100 folds higher in the SCD population comparing to the general population.12 Our study revealed that all SCD patients diagnosed with PE were female (n=5), resulting in a significant difference according to gender (p=0.015). This suggests a possible relationship between patient gender and the likelihood of developing PE. However, the sample size was not large and is susceptible to changes in the future. There was no relationship between patient age and the chance of developing PE, as both SCD patients with PE (mean=38.6) and without PE (mean=37.3) had very similar ages on average.

According to our analysis, no relationship existed between the patients’ Hb and HbS% on admission and the likelihood of developing PE. The majority of SCD patients were admitted for some time in the ward and received simple blood transfusion or exchange transfusion to improve microvascular perfusion. This might have masked the role of the Hb and HbS% level at the time of admission.[26-28] No relationship was found between the length of ICU stay and the likelihood of developing PE, which was statistically nonsignificant in the t-test (p=0.851). Most patients in the ICU were transferred from wards following a couple of days, while others were immediately transferred from accident and emergency departments, depending on illness severity.16

None of the patients who had PE died during their stay in the ICU. This suggests the absence of a relationship between PE development and mortality (p=0.891). Three deaths occurred in the ICU among SCD patients in our study. The first patient was admitted with VOC, the second patient was admitted with drug overdose, and the third patient had VOC on renal replacement therapy due to end- stage kidney disease. Alkhawaja et al16 studied the indices of raised mortality rate in SCD patients were older age, less frequent hospitalization, shorter stay in the ICU and the need for renal replacement therapy. In New York, USA, their study revealed that vital signs, other than an increased respiratory rate, elevated blood urea nitrogen level, thrombocytopenia, high reticluocyte counts, and lower haptoglobin counts were predictors of ICU mortality for SCD patients.29 Similarly, in the UK study, no basic demographics presented a statistically significant association with mortality risk.22 In the Pensylvania, USA study, no distinctive clinical or laboratory parameters were predicted of PE.12

Study limitations

The sample size was not large, which can be overcome in the future by performing prospective research that includes more variables and that is conducted over several years. Our study has some major strengths despite these limitations. First, it is a study describing the incidence and demographic characteristics of SCD patients with PE in Bahrain. Second, the study raises awareness among SCD patients regarding early hospital presentation. Third, it encourages a change in hospital protocols in regard to approaching SCD patients with suspected PE and providing early treatment, which reduces mortality significantly.

In conclusion, SCD is a common hematological genetic disorder in Bahrain. The demographic characteristics included a male predominance, age in the mid-thirties and VOC diagnosed upon admission to the ICU. The incidence of PE was significantly related to female gender. No relationship existed between the likelihood of developing PE and age, Hb and HbS% on admission, length of stay in the ICU, or mortality.

Table 1

Information on patient’s gender and age.

Table 2

Sickle cell disease patients admitted with different diagnoses.

Table 3

Hemoglobin and hemoglobin S% on admission and length of stay in the ICU.

Table 4

Incidence of pulmonary embolism (PE) and gender.