Vitamin k deficiency bleeding presenting as nodular purpura in infancy: a rare and life-threatening entity.

Vitamin K deficiency bleeding (VKDB) disorder is an uncommon entity, which occurs due to inadequate activity of vitamin K-dependant coagulation factors. An 8-months-old exclusively breast-fed male infant presented with multiple, purpuric and nodular non-collapsible swellings on trunk of 4 days duration. Investigations revealed raised activated partial thromboplastin time and prothrombintime. Fibrinogen level and platelet counts were normal. Late VKDB usually presents as intra-cranial or mucosal hemorrhages.([1]) Though skin and mucosal bleeding may occur in 1/3(rd) of infants with VKDB, 'nodular purpura' is not the common presenting feature. Earlier recognition of VKDB and immediate investigation/treatment helps prevent the potentially fatal outcome of the disease. Very little is mentioned about this entity in dermatology literature.

What was known?

Neurological signs and symptoms are the most common presenting features of VKDB. Late VKDB may be fatal with high risk of intra.-cranial hemorrhage. Though petechiae, purpura and/or ecchymoses may be seen in less than 30% of infants with VKDB, they are not the sole presenting features per se.

Introduction

Vitamin K deficiency bleeding (VKDB) is a rare but serious bleeding disorder, which occurs due to inadequate activity of vitamin. K-dependant coagulation factors (Factor II, VI, IX, X).[1] It was earlier known as hemorrhagic disease of the newborn.[12] This en tity is likely to be missed or overlooked because it may mimic relatively commoner diseases such as immune thrombocytopenic purpura, leukemia, and hemophilia. Though a few case series have described the fatal intra-cranial manifestations of VKDB, very little is mentioned about its dermatological manifestations in literature.[23456] Late VKDB is an uncommon entity with incidence of 4 to 10 per 1 lakh live births and occurs mostly in exclusively breastfed infants.[1] Late VKDB is common in Southeast Asia with incidence increasing to 35 per 1 lakh live births in Thailand.[27]

Case Report

An 8-month-old exclusively breastfed male infant presented in casualty with multiple skincolored to bluish, raised swellings on trunk and upper extremities of 4 days duration. This was associated with malena for last 2 days. There was no history of fever, excessive cry, jaundice, bleeding diathesis, vomiting, breathlessness, or any drug intake in recent past. The lesions were acute in onset and progressive in nature. The infant was a product of non-consanguineous marriage and was born at term in a primary health center. There were no perinatal complications. History of vitamin K prophylaxis at birth was not forthcoming. There were two elder healthy male siblings. Mother denied any history of drug intake recently by infant or herself. Cutaneous examination revealed multiple firm to soft, non-collapsible, subcutaneous, non-tender, skin colored to bluish nodules of 1-6.5 cm in diameter on the chest, elbow, and knees [Figures 1 and 2]. General examination revealed a grade III malnourished child (as per classification of Indian Academy of Pediatrics) with normal developmental milestones. General and systemic examination failed to reveal any abnormality, except pallor. Investigations revealed raised APTT and PT levels along with microcytic, hypochromic anemia. Fibrinogen level, platelet count, routine urine microscopy, and other hematological and biochemical parameters were within normal range. Blood culture was sterile, and skin biopsy was not performed as FNAC from a large purpuric nodule revealed frank blood. Vitamin K level estimation could not be done due to financial constraints.

Figure 1

Multiple nodular lesions on right elbow, right knee, and lateral side of chest (Highlighted by black arrows)

Figure 2

Skincolored to purplish nodules on chest wall and right elbow (Highlighted by black arrows)

A provisional diagnosis of late idiopathic vitamin K deficiency bleeding (VKDB) disorder was made, and the child was given 7.5 mg vitamin K1 intra-muscularly once-daily for 3 days. The infant improved dramatically. Prolonged APTT and PT normalized within 10 hours of first dose. All the lesions subsided by 6th day. The infant was put on proper complementary feeding, and no recurrence was noted during follow-up even 6 months after the initial episode.

Discussion

VKBD has been classified based on age of onset as early (occurring within 24 hours of birth); classical (day 1-7 of birth), and late VKDB (1 week to 12 months after birth).[146]

Late VKDB may be idiopathic or secondary.[2] Idiopathic VKDB was described in 1966 as acquired prothrombin complex deficiency (APCD), and majority of cases have been reported from Southeast Asia.[17] Exclusive breastfeeding, in absence of any other cause of vitamin K deficiency, is the main cause implicated in idiopathic variant. Further, studies have shown a key role of low vitamin K level in the mother's breast milk in pathogenesis of APCD syndrome.[7] Late VKDB may be secondary to either diseases associated with mal-absorption of vitamin K (viz-diarrheas, celiac disease, cystic fibrosis) or hepatobiliary diseases associated with decreased synthesis of vitamin K (viz-biliary atresia, α1-anti-trypsin deficiency, hepatitis).[14] VKDB may also result due to antagonism of vitamin K by drugs such as carbamazepine, phenytoin, barbiturates, cephalosporin, rifampicin, isoniazid.[4]

Clinical presentation of late VKDB ranges from life-threatening intra-cranial hemorrhage to skin bleeds with nodular purpura.[23] Neurological signs and symptoms with/without intra-cranial hemorrhage are the most common presenting feature in 50-80% of patients.[15] Nodular purpura is not a common presenting feature. Though skin bleeding in the form of petechiae, purpura, or ecchymoses may occur in 10-30% of patients, it is a presenting feature in only half of such infants.[568] Nasal, gastrointestinal, umbilical, or urogenital bleeding may also occur along with/without seizures, vomiting, poor feeding, altered sensorium. Late VKDB may be fatal, and risk of intra-cranial hemorrhage may be as high as 80%.[19] Subcutaneous tissue bleeding and widespread deep ecchymoses gives rise to characteristic ‘nodular purpura’. It occurs on the lower extremities, back, chest abdomen, buttocks, upper extremities face, and neck in descending order of frequency.[34] These lesions are bluish-violet in color with raised infiltrated purplish centers, and their diameter may vary from 1.5 cm to 7.5 cm.[3] Additionally, hematomas may occur at skin puncture sites.[1]

A clearly prolonged PT (INR > 3.5) or low Quick–value (< 20%) along with normal fibrinogen concentration and platelet count is highly suggestive of VKDB.[1] Circulating acarboxy proteins are present.[1] Anemia and leukocytosis have been reported.[358] Rapid normalization of deranged coagulation time after vitamin K administration confirms the diagnosis.[1] Coagulation time may normalize within 4 hours of vitamin K administration.[1] Skin biopsy is inconclusive and showed only extravasations of RBCs without vasculitis or intravascular thrombosis in a case series.[3] Infants with VKDB should receive 5-10 mg of parenteral vitamin K1. Children with VKDB due to mal-absorption require chronic administration of high doses of oral vitamin K (2.5 mg twice/week to 5 mg/day).[10] A single intra-muscular infection of vitamin K (1 mg) is recommended prophylactically to prevent VKDB.[10]

Purpura fulminans, extramedullary erythropoeisis (Blueberry muffin baby), and protein C or protein S deficiency should be excluded in early and classical VKDB.[4] Consumption co-agulopathies feature reduced fibrinogen and platelet counts.[1] Extremely rare hereditary deficiencies of factors V, VII or X may need to be excluded by analysis of single factors.[1]

To conclude, nodular purpura in infancy should be taken seriously in a breastfed infant as these may denote “warning bleeds,” which may precede potentially fatal intra-cranial bleeding.[6] An infant presenting with nodular purpura requires prompt intervention to avoid impending catastrophe. It has much more clinical relevance in a developing nation like India, where exclusive breastfeeding is continued for very long periods. Further vitamin K prophylaxis is not practiced uniformly in India.[6] As a rare presentation of VKDB, this case report and review of literature is an attempt to make all the dermatologists aware of this potentially life-threatening disease that is easily treatable.

What is new?

Nodular purpura may be a presenting feature of late VKDB. Nodular purpura may precede potentially fatal intra-cranial hemorrhage and hence its presence should prompt treating physician to take adequate remedial steps as soon as possible.