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Bleeding Disorder

Bleeding may occur as a result of qualitative or quantitative defects in platelets.

  1. Platelet count: Normal count 150,000 – 450,000/ml.
    In congenital and acquired thrombocytopenia, the count is low.
  2. Bleeding time: Normal bleeding time is < 8 min;
    In thrombocytopenia and in other platelet disorders, bleeding time is prolonged.
  3. Prothrombin time (PT): It indicates the integrity of extrinsic coagulation pathway.
    Normal PT is 12 – 14 sec. Prothrombin time is prolonged in factors II, V, VI, X deficiency, liver disease, warfarin therapy and DIC
  4. Activated partial thromboplastin time (PTT): It indicates the integrity of intrinsic coagulation pathway. Normal PTT is 30 – 40 sec. PTT is prolonged (60 –85 sec) in deficiency of factors II, V, VIII, IX, X, XI, hemophilia A and B, von Willebrand’s disease and DIC
  5. Fibrinogen level: Normal level is 1.5 – 3.0 gm/dl.
    The level is low in congenital hypofibrinogenemia.
  6. Clot retraction time.
    Abnormal prolongation of clot retraction time indicates platelet function defects like Glanzmann thrombasthenia, Bernard – Soulier syndrome.
Fig 116-1 Coagulation cascade and laboratory assessment of clotting factor deficiency by activated partial prothrombin time (aPTT), prothrombin time (PT), and thrombin time (TT). (Harrison, 18th edition, Pg-974)

Cause of Isolated prolongation of PT
  1. Vitamin K deficiency
  2. Warfarin therapy
  3. Liver disease
  4. Factor VII deficiency
  5. New born (due to Vit K deficiency)
PTT is prolonged with deficiency of factors: XII, XI, IX, VIII, II, I and thrombin
PT is prolonged with deficiency of factors: VII, V, II, I and thrombin
Isolated elongation of aPTT with bleeding manifestations Isolated prolongation of aPTT without bleeding manifestations
Factor VIII defect
Factor IX defect
Factor XI defect
Factor XII defect
Prekallikrein defect
HMW kininogen defect

A prolonged bleeding time in a patient with a normal platelet count is indicative of a qualitative platelet abnormality, von Willebrand disease, or afibrinogenemia. (AIPG 2011)
Disorder Platelet count Bleeding time PT PTT
Thrombocytopenia - -
Hemophilia A or B - - -
Von Willebrand’s disease - -
Vitamin K deficiency - -
Bemard-soulier disease - -
Glanzmann’s thrombasthenia - - -

Extra Edge:

  1. Thrombocytopenia = < 100,000/mm3.
  2. Platelet count must reach a very low value (15,000–20,000/mm3) before generalized bleeding occurs;
  3. The PFA-100, an instrument that measures platelet-dependent coagulation under flow conditions, is more sensitive and specific for platelet disorders and vWD than the bleeding time.
  4. PT (extrinsic)––factors II, V, VII, and X.
  5. PTT (intrinsic)––all factors except VII.
  6. Bernard-Soulier disease = defect of platelet adhesion (↓ GP Ib).
  7. Glanzmann’s thrombasthenia = defect of platelet aGgregation (↓ GP IIb-IIIa).


Hemostatic disorders and coagulation test abnormalities
  1. Prolonged activated partial thromboplastin time (aPTT)
    1. No clinical bleeding – ↓ factors XII, high-molecular-weight kininogen, protein kinase
    2. Variable, but usually mild, bleeding – ↓ factor XI, mild ↓ FVIII and FIX
    3. Frequent, severe bleeding – severe deficiencies of FVIII and FIX
    4. Heparin
  2. Prolonged prothrombin time (PT)
    1. Factor VII deficiency
    2. Vitamin K deficiency – early
    3. Warfarin anticoagulation
  3. Prolonged aPTT and PT
    1. Factor II, V or X deficiency
    2. Vitamin K deficiency – late
    3. Direct thrombin inhibitors
  4. Prolonged thrombin time
    1. Heparin or heparin-like inhibitors
    2. Mild or no bleeding – dysfibrinogenemia
    3. Frequent, severe bleeding – afibrinogenemia
  5. Prolonged PT and/or aPTT not correct with mixing with normal plasma
    1. Bleeding – specific factor inhibitor
    2. No symptoms, or clotting and/or pregnancy loss – lupus anticoagulant
    3. Disseminated intravascular coagulation
    4. Heparin or direct thrombin inhibitor
  6. Abnormal clot solubility
    1. Factor XIII deficiency
    2. Inhibitors or defective cross-linking
  7. Rapid clot lysis
    1. Deficiency of α2-antiplasmin or plasminogen activator inhibitor 1
    2. Treatment with fibrinolytic therapy
Platelet function may be assessed by ‘Bleeding time’ and platelet adhesion assays.

Effects of aspirin Therapy
  1. Ingestion of aspirin significantly prolongs the BT
  2. Aspirin irreversibly inhibits COX –1 and COX – 2. COX inhibition leads to prevention of TXA2 synthesis and impairment of platelet secretion and aggregation.
  3. The effect of aspirin on platelet function occur within 1 hours and lasts for the duration of the affected platelet’s life span i.e. 1 weeks.
Vitamin K Deficiency
  1. Hemorrhagic disease of new born results from a deficiency of vitamin K.
  2. Prothrombin time is the single best laboratory test to detect vitamin K deficiency as vitamin K deficiency may present with isolated prolongation of PT.
  3. Lab features of vit K deficiency
    1. Both PT and PTT are prolonged but prolongation of PT is a more sensitive test to detect vit K deficiency than PTT
    2. The PT is prolonged to a greater extent than PTT
    3. With mild vit K deficiency only the PT is defective
    4. Fibrinogen level, thrombin time and platelet count are not affected.

Extra Edge: (Ref. Hari. 18th ed., Pg- 999)

  1. To calculate the INR, the patient's PT is divided by the mean normal PT, and this ratio is then multiplied by the international sensitivity index (ISI), an index of the sensitivity of the thromboplastin used for PT determination to reductions in the levels of the vitamin K–dependent clotting factors.
  2. Highly sensitive thromboplastins have an ISI of 1.0.
  3. Most current thromboplastins have ISI values that range from 1.0 to 1.4.


Non bleeding disorder/Deficiency of the contact factors
  1. Contact factors function at the step of initiation of intrinsic pathway of the clotting cascade and include the following:
  2. Contact factors are
    1. Factor XII
    2. Prekallikrein
    3. High Molecular Weight Kininogen (HMWK)
  3. Deficiency of these factors is characterized by.
    1. Isolated prolonged of PTT
    2. Absence of clinical bleeding
  4. These patients do not need treatment.
  5. A paradoxical situation in which these is an extremely prolonged PTT but no evidence of clinical bleeding suggests a deficiency of contact factors.

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