Haemophilia A and B, vitamin K deficiency and DIC

Overview

Coagulation (secondary haemostasis) disorders cause deep bleeding: into joints, muscles and after surgery or tooth extraction, often delayed after the injury. This differs from platelet disorders, which give skin and mucosal bleeding.

• Inherited disorders usually involve one factor (haemophilia A, haemophilia B).
• Acquired disorders usually involve several factors (vitamin K deficiency, liver disease, DIC).

Reading the clotting screen

Haemophilia A and B

Genetics

• Both are X-linked recessive: males are affected, females are carriers.
• Carrier mother: each son has a 50% chance of being affected; each daughter a 50% chance of being a carrier.
• Affected father: all daughters are carriers, all sons are normal (no male-to-male spread).
• About one-third of cases arise from a new mutation with no family history.
• In severe haemophilia A, an intron 22 inversion of the factor VIII gene is found in about half of families.
• Some carriers have low factor levels (random X-inactivation) and may bleed.

Differences between A and B

Presentation

Severity depends on the factor level (normal about 50-150 IU/dL):

• Haemarthrosis: knees, elbows, ankles; painful, hot, swollen joint. Repeated bleeds cause chronic arthropathy and deformity.
• Muscle haematomas (e.g. iliopsoas): can compress nerves (femoral nerve) or cause compartment syndrome.
• Bleeding after circumcision, tooth extraction or surgery, often delayed or recurrent.
• Intracranial haemorrhage: the most dangerous bleed.
• Haematuria.

Investigations

Management

• Register with a haemophilia centre; avoid IM injections and antiplatelet drugs; dental care.
• Factor replacement (recombinant preferred; plasma-derived used where cost limits supply):
  • On demand: factor concentrate given early for any bleed.
  • Prophylaxis: regular infusions (several times a week for A, about twice a week for B) from early childhood to prevent joint damage.
  • For surgery, keep levels normal until healing (factor VIII often given twice daily because of its short half-life).
• Desmopressin in mild haemophilia A: releases stored factor VIII and vWF (3-5 fold rise). Not effective in haemophilia B.
• Tranexamic acid for mucosal and dental bleeding.
• Emicizumab: a bispecific antibody that bridges factors IXa and X, mimicking factor VIII; given subcutaneously as prophylaxis in haemophilia A (with or without inhibitors).
• Joint bleeds: factor replacement, rest, ice, splint, then physiotherapy.
• Cryoprecipitate (contains factor VIII) or FFP (contains all factors, including IX) only where concentrates are not available; FFP is the fallback for haemophilia B because cryoprecipitate lacks factor IX.
• Gene therapy is an emerging option.

Complications

• Inhibitors (alloantibodies to factor VIII): develop in up to 30% of severe haemophilia A, usually early in treatment. Bleeds are treated with bypassing agents: recombinant factor VIIa or activated prothrombin complex concentrate. Long-term: immune tolerance induction.
• Haemophilic arthropathy, muscle contractures.
• Transfusion-transmitted infection (hepatitis C, HIV) in those treated with older plasma products; now rare.

In Pakistan, recombinant products may not always be available; plasma-derived concentrates, cryoprecipitate or FFP may be used. Follow the current national or local haemophilia guidance.

Vitamin K deficiency

Role of vitamin K

Vitamin K (fat-soluble) lets the liver gamma-carboxylate glutamic acid residues on clotting factors II, VII, IX, X as well as the natural anticoagulants protein C and protein S. Proteins that miss this step cannot bind calcium, so they stay inactive. Warfarin blocks vitamin K epoxide reductase, which recycles vitamin K.

Aetiology

Vitamin K deficiency bleeding of the newborn

• Early: first 24 hours (often maternal drugs such as anticonvulsants or warfarin).
• Classical: days 2-7; bruising, gut or umbilical bleeding; mostly exclusively breast-fed babies.
• Late: weeks to months after birth; can cause intracranial haemorrhage.
• Prevented by giving vitamin K 1 mg IM to every newborn at birth.

Laboratory findings

• PT/INR prolonged first and most (factor VII has the shortest half-life), then APTT prolonged too.
• Platelets, fibrinogen and bleeding time normal.
• Correction of PT after parenteral vitamin K confirms the diagnosis.

Management

• Vitamin K (phytomenadione) 10 mg IV for bleeding in adults; PT starts to correct within about 6 hours but may take up to 2 days.
• Major or life-threatening bleeding: give prothrombin complex concentrate (PCC) (or FFP if PCC unavailable) plus IV vitamin K.
• In cholestasis give vitamin K parenterally (oral is poorly absorbed).
• Treat the cause.

Disseminated intravascular coagulation (DIC)

Definition and pathophysiology

DIC is widespread activation of coagulation inside blood vessels. It is never a primary disease: always secondary to an underlying disorder.

1. Tissue factor or other procoagulants enter the blood (or cytokines activate endothelium).
2. Fibrin is laid down in small vessels → microthrombi, organ ischaemia (skin, brain, kidneys).
3. Platelets and clotting factors are consumed → bleeding.
4. Secondary fibrinolysis makes fibrin degradation products and D-dimer, which further impair clotting.
5. Red cells are cut by fibrin strands → schistocytes (microangiopathic haemolysis).

Aetiology

Clinical features

• An acutely ill, often shocked patient with an obvious underlying cause.
• Bleeding from venepuncture and cannula sites, wounds, mouth, nose, gut; widespread ecchymoses.
• Thrombosis: skin necrosis, digital gangrene, purpura fulminans, renal failure, confusion, lung injury.
• Chronic DIC (e.g. cancer, dead fetus) may show mainly thrombosis with mild lab changes.

Diagnosis and lab abnormalities

ISTH scoring (used only when an underlying cause is present):

A total of 5 or more fits overt DIC (repeat daily); under 5 suggests non-overt DIC (repeat in 1-2 days).