Hereditary hemorrhagic diseases

Dr Micheline Birac
MD/Hospitalist at Mount Lebanon Hospital
Hemophilia
 Definition
• A deficiency of a clotting factor that leads to a bleeding condition.
Subtypes are distinguished on the basis of which factor is lacking.
See table 2 .
• The condition is usually hereditary but may be acquired through
the development of an antibody to a clotting factor. This may occur
in patients with autoimmune or lymphoproliferative disease,
postpartum or following a blood transfusion.
• Patients are nearly always male and may have a positive family
history.
 Types of hemophilia (table 2)

Subtype
Hemophilia A (factor VIII deficiency) (90 %)
Hemophilia B (factor IX deficiency) (9%)
Hemophilia C (factor XI deficiency ) (< 1%)
Factor VII deficiency(< 1%)
Pathogenesis
X-linked inheritance; the most common severe
congenital clotting deficiency
X-linked inheritance
Most common in Ashkenazi Jews
Presents in a milder, likely heterozygous form.
 History
• Presents with spontaneous hemorrhage into the tissues and
joints that, if left untreated, can lead to arthropathy and joint
destruction.
• Spontaneous intracerebral hemorrhages, renal and
retroperitoneal bleeding and GI bleeding may also be seen.
• Mild cases may have major hemorrhage after surgery or
trauma but are otherwise asymptomatic.
 Diagnosis
• Evaluate for suspected clotting factor deficiency
– PT: usually normal but isolated elevations are seen in congenital factor VII deficiency
– PTT :prolonged (the more prolonged the more severe the hemophilia)
– Thrombin time, fibrinogen, bleeding time: usually normal
• Conduct a mixing study: mix the patient’s plasma with normal plasma; if this
corrects the PTT, a factor deficiency is likely. If the PTT des not correct, the
patient may have a clotting factor inhibitor.
• Obtain factor assays: Specific factor assays should then be performed for factors
VII VIII IX XI XII. Hemophilia is characterized according to factor level as follows:
– Mild ˃ 5% of normal
– Moderate 1-3 % of normal
– Severe ˂ 1% of normal
 Treatment
• Treat bleeding episodes with immediate transfusion of clotting factors (or
cryoprecipitate) to at least 40% of normal concentration. Factor VIII has a
half life of 12 hours, so patients should be dosed BID to maintain adequate
levels. Factor IX has a half life of 24 hours, so daily transfusion is needed.
• The length of the treatment varies with the lesion, extending up to several
weeks after orthopedic surgery.
• Mild Hemophilias may be treated with desmopressin; if so, they should be
fluid restricted to prevent the side effect of hyponatremia.
• It may be necessary to transfuse RBCs depending on the degree of blood
loss.
Von Willebrand’s Disease
 Definition

• An autosomal dominant condition in which patients have

deficient or defective von Willebrand’s factor (vWF) with low
levels of factor VIII which is carried by vWF. Symptoms are due
to platelet dysfunction and to deficient factor VIII. The disease
is milder than hemophilia.

• vWD is the most common inherited bleeding disorder (1% of

the population is affected)
 Physical Examination

• Patient presents with

– Easy bruising
– Mucosal bleeding (epistaxis or oral bleeding)
– Menorrhagia,
– Postincisional bleeding
• Platelet dysfunction is not severe enough to produce
petechiae.
• Symptoms worsen with ASA use (eg aspirine)
 Diagnosis

• Look for a family history of bleeding disorders

• Platelet count and PT are normal but a prolonged PTT may be
seen as a result of factor VIII deficiency.
• A ristocetin cofactor assay of patient plasma can measure the
capacity of vWF to agglutinate platelets.
 Treatment

• Bleeding episodes can be treated with DDAVP (a vasopressine like

an antidiuretic hormone developped to treat diabetes)

• Menorrhagia can be controlled with OCPs (oral contraceptive pills)

• Avoid ASA ( acetylsalicylic acid eg aspirine) and other inhibitors of

platelet function.