Internal Diseases and Therapy · MU Sofia

72. Hemorrhagic diathesis – normal hemostasis. Hemophilia

Explains haemophilia as an inherited, X-linked recessive bleeding disorder, distinguishing type A (factor VIII deficiency) from type B (factor IX deficiency) and their place in the intrinsic pathway. It gives incidence figures, the genetic basis of mutations and carrier effects through lyonization, with an inheritance diagram. Severity is graded by clotting factor level, followed by diagnostic steps, a list of differentials and management of acute bleeding and prophylaxis.

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Topic 73 of 139 in the MU Sofia syllabus for Internal Diseases and Therapy (Medicine, Years 4 and 5). The free AceMed note covers it in 1 section, about 364 words (2 min of reading), with 15 flashcards.

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  1. Hemorrhagic diathesis - classification. Haemophilia

Hemorrhagic diathesis - classification. Haemophilia

See above for classification of hemorrhagic diathesis.

Haemophilia

Haemophilia is an inherited bleeding disorder, with an X-linked recessive pattern of inheritance. Haemophilia has two types, A and B. A results from the deficiency of clotting factor VIII, while B results from the deficiency of clotting factor IX. Both factor VIII and IX are part of the intrinsic pathway (see coagulation cascade below).

Incidence of haemophilia A is about 1 in 5000 boys/men while haemophilia B is about 1 in 30,000. Interestingly, despite all official haemophilia sufferers are male, about 30% of female haemophilia carriers have clotting factor levels in the haemophilia range due to lyonization (random inactivation of the normal X chromosome).

Image: “X-linked recessive (2)” by File:Autosomal recessive - en.svg : Domaina , Kashmiri and SUM1 Derivative work: SUM1, CC BY-SA 4.0, via Wikimedia Commons.

Both factor VIII and IX genes are on the long arm of chromosome X. 50% of mutations for haemophilia A are the result of intrachromosomal inversions involving regions in the introns 1 and 22 of the factor VIII gene. The remaining cases are due to deletions, insertions, missense or nonsense point mutations.

The pathophysiology is very simple, loss of the clotting factor means worse clot formation (due to reduced thrombin generation), which means unstable clot and excessive bleeding. Haemophilia A and B can be categorised by severity, based upon the plasma levels of factor VIII and IX:

  • Severe <1% clotting factor level (CFL) - frequent spontaneous bleeding, particularly into joints and muscles
  • Moderate 1-5% CFL - occasional spontaneous bleeding, severe bleeding with trauma/surgery
  • Mild - 5-40% CFL - severe bleeding with trauma and injury

Diagnosis is based on clinical suspicion (recurrent bleeding, especially into joints in children +/or FH). Investigate aPTT, if raised, perform factor VIII and/or factor IX assay.

Differentials include:

  • Von Willebrand Disease
  • Platelet dysfunciton
  • Deficiency of tother coagulation factors
  • Ehlers-Danlos
  • Scurvy
  • Fabry’s disease
  • Child abuse
  • DIC

Management

  • Acute bleeding episode
  • Factor VIII or IX replacement by infusion or concentrate
  • Antifibrinolytic agents (eg. aminocaproic acid)
  • As prophylaxis, regular IV replacement of factor VIII and IX is indicated, for at least 45 weeks/year to prevent bleeding. This should be started as young as possible in the child.

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