Bleeding Disorders

Bleeding disorders 1Bleeding disorders 2Bleeding disorders 3Bleeding disorders 4

 


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

 

Bleeding disorders 5

 


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)

 


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

 


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

 

Bleeding disorders 6
Indications for platelet transfusion

 


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

 


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

 


Download the PDF version: here


References:

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

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