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Disorder due to Deficiency of Clotting Factors

Hemophilia A

Reduction of factor VIII results in hemophilia A.
Factor VIII is synthesized by the liver primarily and also by spleen, kidney and placenta. It is bound to the von Willebrand factor (vWF)
Hemophilia is a X – linked disorder. 
Hemo A (classical hemophilus) Hemo B (Christmas disease)
1 defect ¯ VIIIC ¯ IX
2 pathway Intrinsic Intrinsic
3. CT, PTT ­ ­
4. PT, BT N N

Clinical Features

  1. The normal factor VIII level is 50 – 100% (0.5 – 1.5 U/mL) and is usually measured by a clotting assay.
  2. If factor VIII level is < 2%, patient presents with recurrent, spontaneous (LQ 2012) hemarthrosis which later leads to osteoarthritis, muscle hematomas involving calf and psoas muscles (it may lead to compression of femoral nerve and paraesthaesia in thigh and weakness of the quadriceps and contraction and shortening of the Achilles tendon).
  3. If factor VIII level is 2 – 10%, mild trauma or surgery may cause haematomas.
  4. If the factor VIII level is 10 –50%, major injury and surgery may cause excessive bleeding.


  1. Arthropathy
  2. Muscle atrophy (due to haematomas)
  3. Mononeuropathy (compression by haematomas)
  4. Risk of hepatitis (B, C, D) and HIV through blood and blood product administration.
  5. Pseudotumors syndrome
  6. Pseudo phlebitis
  7. Compartmental syndrome


  1. Bleeding episodes are treated by factor VIII concentrate infusion (from donor plasma).
  2. IV desmopressin 0.3 mg/kg, can be given to raise factor VIII level to three to five fold.
  3. Cryoprecipitate is rich in factor VIII concentrate
  4. Antifibrinolytic drugs - E amino caproic acid (EACA), Tranexamic acid
Haemophilia B (Christmas Disease)
Aberration of the factor IX gene, present on X chromosome, results in a reduction of factor IX level, giving rise to haemophilia B.
Factor IX concentrate. 
Haemophilia A (Classical hemophilia) Haemophilia B (Christmas disease)
Pathway of coagulation affected
Whole blood clotting time
Platelet count
Tourniquet test
Deficiency of coagulant subunit of factor i.e. (VIII C)
Factor VIII = VIII c + VWF
Intrinsic pathway
Deficiency/absence of factor IX.
Intrinsic pathway

Von willebrand’s disease

  1. von Willebrand’s disease (vWD) is a common hereditary bleeding disorder. 
  2. It is characterized by a prolonged BT and reduced factor VIII – C levels between about 10 –40%. 
  3. Joint bleeding is rare. 
  4. The gene for von Willebrand’s factor (vWF) is located on chromosome 12 and is inherited as an autosomal disorder. 
  5. Type I, II and IIB are autosomal dominant type. IIC and III are autosomal recessive.  (Autosomal hemophilia – New Name)
Clinical Features
Superficial bruising, epistaxis, menorrhagia and GI bleeding are common especially after trauma or surgery. 

The diagnostic pattern consist of:
  1. Prolonged bleeding time and prolonged clotting time.
  2. Reduced plasma vWF concentrations
  3. Reduction in biological activity as measured by ristocetin cofactor assay (P) aggregation in response to ristocetin is
  4. Reduced factor VIII activity. 
Note: Von Willebrand's disease: Platelet aggregation studies with standard agonists ADP, collagen, thrombin are normal but platelet aggregation in response to ristocetin may be subnormal

  1. Reduced level of vWF            
  2. Secondary reduction in factor VIII    
  3. Prolongation of the bleeding time.
  1. Desmopressin
  2. Factor VIII – C concentrates (contain adequate vWF also)
  3. Cryoprecipitate: It contains all of the vWF multimers. It is the safest and most cost – effective modality of treatment. 
  4. Platelet transfusions for cases with uncontrolled bleeding
  5. Fresh frozen plasma (FFP) can be given for mild disease. 
Property VWF Factor VIII
Gene Located on chromosome XII Located on X chromosome
Inheritance Autosomal dominant Sex linked
Synthesis Endothelial cells, megakaryocytes platelets (not in liver cells) In liver cells
Function Facilitate the adhesion of platelets to subendothelial collagen Activation of factor X in coagulation cascade
Disease V. W. disease Hemophilia

Features of VWF and differences with hemophilia A
Feature Hemophilia A Von Willebrand Disease  
1.  Inheritance
x- linked recessive Autosomal dominant
2.  Factor VIIIc
Decreased  Normal
3.  VWF
Normal  Decreased
4.  Common Presentation Features of clotting disorder
Skin/Mucosal bleeding -
Hemarthrosis ++
 Features of bleeding disorder ± clotting disorder
 Skin/Mucosal bleeding +
5.  Bleeding Time Normal  Prolonged
  6.  APTT Prolonged Prolonged (may be normal)
  7.  PT Normal Normal
8.  Thrombin Time Normal Normal
  9.  Fibrinogen Normal Normal
10.  Platelet aggregation in
Response to Ristocetin
Normal Decreased

Important Points::
Parahemophilia: AR, Factor V deficiency, ­  ↑ PT, ­  ↑ PTT
Hemophilia C: XI deficiency , AR, aPTT is increased,  PT is normal

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