Bleeding Disorders

 

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Evaluation of Bleeding Disorders: 

Platelet type bleeding: (vWD)

• Petechiae, purpura, ecchymoses, bruising
• Menorrhagia, hematuria, occult GI bleed
• Gingival bleeding, epistaxis

 

Clotting factor type bleeding: (hemophilia)

• Deep bleeding, hemarthrosis, organs bleeding, CNS bleeds
• Ecchymoses, hematoma

 

Lab work:

• BT -> plt function
• PTT -> common (F10, 2, 1) and intrinsic pathway (F12, 11, 9, 8)
• PT -> common (F10, 2, 1) and extrinsic pathway (F7, 13), related to INR
• Mixing studies:
  • If corrected -> deficiency
  • If not corrected\partially corrected -> inhibitor (heparin)
  • If more prolonged w\ clinical bleeding -> antibody
  • If more prolonged w\out clinical bleeding -> lupus anticoagulant

 

 

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a. Clotting Factors Disorders:

1. Hemophilia: 

• Hemophilia A: XLR -> deficiency of F8 -> replace F8 + desmopression
• Hemophilia B: XLR -> deficiency of F9 -> replace F9
• Hemophilia C: AR -> deficiency of F11 -> replace F11
• Labs: ↑ PTT + N PT + N BT (bc all three type of hemophilia affect the intrinsic pathway factors)

 

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b. Qualitative Disorders of the Platelets:

1. Von Willebrand’s disease:

• Autosomal dominant -> deficiency of vWF (responsible for the initial adhesion of plts w\ GpIb)
• Labs: ↑ BT (as w\ any plt disorder), ↑ PTT -> (vWF acts to carry\protect F8), normal PT
• Dx: Ristocetin cofactor plt test (quantitative assay for vWFAg, vWF activity) -> in normal people, adding ristocetin will cause aggregation between vWF + GpIb. In pts w\ deficient vWF -> won’t cause aggregation. However, when you add normal serum (which has vWF) -> it will be corrected, and you’ll get normal aggregation
• Tx: Desmopressin, avoid aspirin and NSAIDS, replacement of vWF + F8

 

2. Bernard-Soulier syndrome: 

• Autosomal recessive -> abnormal GpIb (responsible for the initial adhesion of plts w\ vWF)
• Labs: ↑ BT (as w\ any plt disorder), normal PT\PTT
• Dx: Ristocetin cofactor plt test -> won’t cause aggregation. But unlike vWD, adding normal serum won’t correct it
• Tx: supportive

 

3. Glanzmann’s throbasthenia: 

• Autosomal recessive or acquired -> abnormal GpIIb\IIIa (responsible for binding fibrinogen to form the initial clot -> fibrin mesh)
• Labs: ↑ BT (as w\ any plt disorder), normal PT\PTT
• Dx: Ristocetin cofactor plt test -> normal aggregation
• Tx: supportive

 

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c. Quantitative Disorders of the Platelets: 

1. Idiopathic thrombocytopenic purpura (ITP): 

• Acute thrombocytopenia due to autoimmune removal -> autoantibodies against plt surface
• Typically: child, after non-specific viral infection, normal PE (no hepatosplenomegaly or LAP) -> sudden “platelet type bleeding” -> resolving w\in 7 mo (some develop chronic ITP\intracranial hemorrhage)
• Labs: isolated thrombocytopenia (plt count < 20,000), maybe ↑ megakaryocyte in BM biopsy, everything else is normal (N other cell lines, peripheral smear)
• Tx: prednisone, IVIG (if very low plt + ongoing bleeding), splenectomy (if refractory). Plt transfusion is contraindicated!

 

2. Thrombotic thrombocytopenic purpura (TTP): 

• Deficiency of ADAMTS12 (vWF metalloprotease) -> ↓ degredation of vWF multimers -> large vWF multimers -> ↑ plt adhesion -> ↑ plt aggregation + thrombosis
• Sx: neurological and renal symptoms, fever, jaundice
• Dx: schistocyte in peripheral smear (microangiopathic hemolytic anemia), ↑ LDH, N PT\PTT
• Tx: plasmapheresis

 

3. Hemolytic uremic syndrome (HUS): 

• (1) Thrombocytopenia + (2) microangiopathic hemolytic anemia + (3) acute renal failure
• Typically: child, diarrhea (enterohemorrhagic E coli, shiga toxin)
• Labs: thrombocytopenia, ↑ BT, ↑ bilirubin, N PT\PTT, schistocyte
• Same spectrum as TTP: similar presentation and Tx

 

 

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e. Other Bleeding Disorders:

1. Disseminated intravascular coagulation (DIC): 

• Widespread activation of clotting -> exhausts platelets and clotting factors -> bleeding
• Causes: sepsis, trauma, malignancy (M3 AML), nephrotic syndrome, transfusion
• Labs: schistocytes, ↓ plt, ↑ PT\PTT, ↑ D-dimer (fibrin degradation product), ↓ fibrinogen + F5, 8

 

2. Vitamin K deficiency: 

• Newborns (need administration of vit K IM), dec intake, malabsorption
• Dec in vit K-related factors: F2, 7, 9, 10, Proteins C + S
• Labs: ↑ PT + PTT, normal BT + plt count

 

3. Liver disease:

• All clotting factors are exclusively produced in the liver, except F8
• Tx: FFP (all clotting factors), cryoprecipitate (fibrinogen)

 

4. Heparin-induced thrombocytopenia:

• Recent hx of heparin -> development of IgG abs against heparin-bound platelet factor 4
• Widespread thrombosis (DVT, PE)

 

5. HELLP syndrome:

• Obstetrical, pregnant, hx of preeclampsia
• Hemolysis, Elevated Liver enzymes, Low Platelet count

 

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f. Hypercoagulation Disorders:

1. Anti-thrombin deficiency:

» Anti-thrombin normally blocks the activation of F 10, 2

• Inherited deficiency of anti-thrombin -> diminishes the increase in PTT following heparin
• Acquired (renal failure\nephrotic) -> anti-thrombin loss in urine -> ↑ activity of F10, 2

 

2. Factor 5 leiden:

» Normally F5 is deactivated by protein C, and normally it activates F2

• Production of mutant F5 that is resistant to degradation by activated protein C

 

3. Protein C or S deficiency: 

» Proteins C and S normally blocks the activation of F5, 8

• ↑ risk of thrombotic skin necrosis w\ hemorrhage after administration of warfarin

 

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Download the PDF version: here

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References:

• Kaplan lecture notes
• Paul Bolin’s vids
• First aid USMLE step 1