Coagulopathies

Question 1

Hemophilia A (Factor 8)

Answer 1

Inheritance: X-linked recessive
Gene: F8, 30% of mutations are de novo

●Clinically indistinguishable from Hemophilia B
●Diagnosis is based on clotting factor assay
●Excessive bleeding
●Renewed bleeding after initial bleeding stops
●Deep-muscle, intracranial, GI tract bleeds without obvious trauma
●Poor wound healing
●Menorrhagia in symptomatic female carriers
●Excessive bruising, deep-muscle hematomas
●Chronic joint disease from frequent bleeds which can lead to disability

Heterozygous females may be affected, important to assess coagulation factor levels in blood

Treatment:
●Regular Factor VIII intravenous infusions
●Acute treatment with DDAVP

Question 2

Hemophilia B (Factor 9)

Answer 2

Inheritance: X-linked recessive
Gene:F9

●Clinically indistinguishable from Hemophilia A
●Diagnosis is based on clotting factor assay
●Excessive bleeding
●Renewed bleeding after initial bleeding stops
●Deep-muscle, intracranial, GI tract bleeds without obvious trauma
●Poor wound healing
●Menorrhagia in symptomatic female carriers
●Excessive bruising, deep-muscle hematomas
●Chronic joint disease from frequent bleeds which can lead to disability

Heterozygous females may be affected, important to assess coagulation factor levels in blood

Treatment:
●Regular Factor IX intravenous infusions
●Acute treatment with DDAVP

Question 3

Factor V Leiden Thrombophilia

Answer 3

Inheritance: Autosomal Dominant
Gene:F5, “Leiden” refers to the common allele c.1691G>A (p.R506Q)

●Increased risk for venous thromboembolism
oSignificantly increased/likelihood for multiple VTE events in homozygotes
oSlightly increased in heterozygotes

Treatment with long-term oral anticoagulants is necessary, particularly in homozygotes
Possible to be heterozygous for multiple coagulopathies, which increases risk cumulatively

Question 4

von Willebrand Disease

Answer 4

Inheritance: Autosomal dominant (most), AR
Gene:VWF

●Mild to moderate mucocutaneous bleeding
oEasy bruising, nosebleeds, heavy periods
● Type 1 (30%), Type 2 (60%), Type 3(<10%, severe)
oTypes 2B and 2N may have thrombocytopenia
oType 2N has more severe bleeding and mimics hemophilia