“Haemorrhagic disease of the newborn” 89 years later than expected: vitamin K deficiency bleeding

Abstract

A man presented to the emergency department on his 89th birthday in early 2013 with 2 days of persistent bleeding from a minor scalp laceration sustained during a mechanical fall at home. He had undergone elective carpal tunnel release surgery 1 week before, which was followed by progressive swelling and bruising of the left hand. He had a history of idiopathic bile acid malabsorption diagnosed on selenium homocholic acid tauroselcholic acid (SeHCAT) scan, and was taking cholestyramine and vitamin D replacement but no other medication. On examination he had no bleeding from any site other than the scalp wound. CT head showed no intracranial bleed. Blood tests showed anaemia with a polychromatic fi lm, in keeping with haemorrhage. Platelet count and white cell count diff erential and morphology were normal. The prothrombin time (PT) was long (>180 s; normal 12·5 –15·1 s), as was the activated partial thromboplastin time (APTT) (132·5 s; 23·0–37·0 s). Thrombin time (TT) was normal. A 50:50 mix of normal plasma with patient plasma corrected APTT to normal, in keeping with clotting factor defi ciency rather than an inhibitor or lupus anticoagulant. We diagnosed vitamin K defi ciency, stopped the patient’s cholestyramine, and started 10 mg intravenous vitamin K immediately, then daily for three consecutive days. In view of the active bleeding we gave one dose of prothrombin complex concentrate (PCC) 30 units/kg (composed of the vitamin K dependent clotting factors II, VII, IX, and X in a lyophilised, virally inactivated formulation) and 2 units of packed red cells for symptomatic anaemia. Repeat coagulation studies taken 20 min after PCC showed PT and APTT were normal. Bleeding stopped immediately after PCC treatment, and the patient was discharged home 5 days later. Vitamin K defi ciency was confi rmed by severe defi ciency of clotting factor II (2%; normal 50–200%), factor VII (3%; 50–200%), factor IX (6%; 50–200%), and factor X (1%; 50–200%), with preserved clotting factors V, VIII, XI, and XII. Protein Induced by Vitamin K Absence II (PIVKA-II) was greater than 10 au/mL (normal 0·0–0·2 au/mL), in keeping with vitamin K defi ciency. The patient was also defi cient in fat soluble vitamin A (0·90 umol/L; 1·40–3·84), but not vitamin E or D. We prescribed watersoluble oral vitamin K replacement (menadiol sodium phosphate) to prevent further episodes of bleeding, which the patient is still taking. At last follow-up in May, 2014, he remains well, without symptomatic bleeding and with normal PT and APTT. Vitamin K is necessary for the hepatic synthesis of coagulation factors II, VII, IX, and X. Its importance in haemostasis was identifi ed by Danish scientist Henrik Dam in 1929. Investigating the role of cholesterol by feeding chickens a cholesterol-depleted diet, he noticed that chickens kept on this diet developed bleeding. He attributed the bleeding to defi ciency of a vitamin, which he named “Koagulationsvitamin”, later shortened to “vitamin K”. Vitamin K is a fat soluble vitamin, absorbed in the terminal ileum, and is dependent on functioning villi, bile acid, and fat absorption. Cholestyramine is a bile acid sequestrant used in the management of bile acid malabsorption. Both bile acid malabsorption and cholestyramine can be associated with vitamin K defi ciency. “Haemorrhagic disease of the newborn” (now called vitamin K defi ciency bleeding), has been reported since the late nineteenth century. Vitamin K prophylaxis for neonates, recommended since the 1960s, is supported by a Cochrane review. The UK national programme of vitamin K replacement at birth is associated with a decrease in the incidence of vitamin K defi ciency bleeding, most importantly intracranial haemorrhage, with associated improvements in perinatal mortality, and short-term and long-term morbidities (1·2 to 1·8 per 100 000 births). In patients with bile acid malabsorption and those taking c holestyramine, defi ciency of all fat soluble vitamins (K, A, D, and E) should be considered and replaced appropriately.