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
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
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
