MDS: Senior Clerkship 2001/02

Bleeding Disorders.

Bleeding Disorders

Hemostasis:
o Primary:
Adhesion to collagen in subendothelium 
Release of ADP & thromboxane A2  Aggregation of Plts (Plts plug).
o Secondary: extrinsic + intrinsic + common pathways.

Tests of hemostasis:

Platelets:
o #: count, estimate. = 150 – 400 X 109/L.
o Bleeding time: affected by Plts count, Plts function, blood vessels.
o Blood film: if big  new cells.

Coagulation:

aPTT (activated Partial Thromboplastin Time):

o Purpose: measure intrinsic pathway (Factors VIII, IX, XI, XII).
o Normal = 25 sec.
PT (Prothrombin Time):
o Purpose: measure extrinsic pathway (Factors VII; synthesized in liver).
o Normal = 12 sec.
INR (International Normalized Ratio):
o = (PT of pts) / (PT of the normal people).
o Purpose: enables doctors to obtain appropriate level of coagulation,
independent of lab reagents & to follow published recommendations for
intensity of anti-coagulation.
o Normal = 1.

Others:
 Fibrinogen.
 FDP (Fibrinogen Degradation Products)  esp. D-dimers.
 Specific factor assays.
 Tests of physiological inhibitors (anti-thrombins, protein S, protein C,
hereditary resistance to Activated Protein C “APC” = Factor V Leiden).
 Tests of pathological inhibitors (lupus anti-coagulant).

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 MDS: Senior Clerkship 2001/02
Bleeding Disorders.

Signs & symptoms of Disorders of Hemostasis:

Primary (Plts) Secondary (Coagulation)

Surface cuts Excessive, prolonged. Normal / slightly prolonged.
Onset after injury Immediate Delayed
Typical type & site of Superficial: Deep =
bleeding Large spreading ecchymotic
Mucosal:
lesions & hematoma.
 Nasal  epistaxis.
Into joints (hemoarthrosis).
 Gingival.
GU tract.
 GI tract.
Post-traumatic.
 Uterine  menorrhagia.
Petechiae.
Purpura

Classification of Bleeding Disorders:

I. Disorders of Primary Hemostasis:

1. Vascular (Non-thrombocytopenic pupura):

 Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu).

 Acquired:

o Senile purpura: common.

o Dysproteinemias.
o Henoch-Schönlein purpura (HSP).
o Scurvy: due to Vit C deficiency.
o Cushing’s synd.
o Infections.
o Drugs: Steroids.

2. Platelets:
 Dysfunction:

o Hereditary: von Willebrand’s disease.

o Acquired:
 Drugs: ASA, EtOH (alcohol), NSAIDs.
 Uremia.
 Myelo-proliferative disorders.
 Dysproteinemias.

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MDS: Senior Clerkship 2001/02
Bleeding Disorders.
N.B. ASA inhibits Thromboxane A2 (strong inducer of Plts aggregation).
N.B. Uremia also ↓ RBCs lifespan  hemolysis.

 Thrombocytopenia (usually acquired):

o ↓ Production:
 Drugs, toxins.
 Radiation.
 BM infiltrate / failure.
 Megaloblastic anemias (Vit B12, folic acid).
 Myelodysplasia.
 Viral infections (varicella, mumps, HIV, EBV, CMV, parvovirus).
o ↑ Destruction:
 Drugs (quinidine, sulfas, thiazides, heparin, cephalosporins).
 Idiopathic Thrombocytopenic Purpura (ITP).
 Allo-Antibodies: e.g. SLE.
 Infections: HIV, Sepsis.
o ↑ Consumption:
 DIC.
 Micro-angiopathic (Thrombotic thrombocytopenic purpura = TTP).
 Hyper-splenism.

o Sequestration  splenomegaly.

o Dilutional  massive transfusion with stored blood.

II. Disorders of Secondary Hemostasis:

 Hereditary:
o Factor VIII: Hemophilia A + vWD.
o Factor IX: Hemophilia B (Christmas disease).
o Factor XI (Rosenthal synd).

 Acquired:
o Liver disease.
o DIC.
o Vit K deficiency.
o Anti-coagulants: Warfarin (Coumadin).

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MDS: Senior Clerkship 2001/02
Bleeding Disorders.

Specific diseases

Idiopathic Thrombocytopenic Purpura (ITP):

Child type (acute):

 Cause: Antibodies (Abs) that bind to Plt membranes  splenic destruction

of Ab-coated Plts.
 Presentation:
• Typically present after viral illness.
• Sudden onset of petechiae, purpura, epistaxis in otherwise healthy child.
• Negative signs: no lymphadenopathy, no hepatosplenomegaly.
• If atypical presentation (> one cell line is abnormal, hepatosplenomegaly) 
rule out leukemia  do BM aspiration.
 Self-limited in 80% children, but usually treat because spontaneous recovery
takes a few months.
 DDx:
o Leukemia.
o Drug-induced thrombocytopenia.
o Infection (viral).
o SLE.
o HIV.
 Labs:
o Thrombocytopenia (Plts < 20 X 109/L).
o Normal WBC & RBC.
 Mx:
o IVIg.
o Prednisolone  rule out leukemia before using it!
o For life threatening bleeding  Splenectomy.

Adult type (chronic):

 Commonest cause of isolated thrombocytopenia.

 Pathophysiology: IgG auto-Abs.

Features Acute ITP Chronic ITP

Peak age 2-6 yrs 20-40 yrs
Sex predilection None >♀
Hx of recent infection Common Rare
Onset of bleed Abrupt Insidious
Plt count < 20 X 109/L 30-80 X 109/L

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MDS: Senior Clerkship 2001/02
Bleeding Disorders.

Duration Weeks Months – yrs

Spontaneous remissions > 80% uncommon

Hemorrhagic disease of newborn:

 Cause: Vit K deficiency  ↓ Factors II, VII, IX, X (mnemonic: 1972),

Protein C, Protein S ↑ PT & aPTT.
 Presents at 2-7 days with bleeding: GI, intracranial, bleeding from
circumcision or umbilical stump.
 Prevention: IM Vit K at birth to all newborns.

Hemophilia: (very important)

Hemophilia A:

 X-linked recessive, >> common than Hemophilia B.

 Cause: Factor VIII deficiency  delayed formation of Thrombin (important
in forming normal functional fibrin clot & solidifying Plt plug at areas of
vascular injury).
 Severity
o Depends on:
 Level of factor VIII.
 Severity of bleeds.
 Presence of Abs to factor VIII.
o Mild (>5% factor VIII):
Bleeding: GI, GU, after significant trauma (e.g. surgery).
o Moderate: (1-5% of Factor VIII).
o Severe (<1% factor VIII): spontaneous bleeding / bleeding from minor
trauma. Hallmark is hemoarthrosis.
 Lab:
o ↑ PTT + Normal INR (PT).
o ↓ Factor VII.
o vWF: normal.
 Rx:
o Factor VIII replacement: for minor / major trauma, prophylaxis.
o DDAVP for mild disease.

Hemophilia B = Christmas disease:

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MDS: Senior Clerkship 2001/02
Bleeding Disorders.

o Factor IX deficiency.
o XR.
o Presentation: same as Hemophilia A.
o Rx: Factor IX replacement.

von Willebrand disease:

 Normal: von Willebrand factor is adhesive protein 
o Enhances Plts adhesion to subendothelial collagen.
o Protects factor VIII from rapid clearance.
 Abnormal: defect in vW factor.
o AD (> common, mild) + AR (rare, severe).
o Both 1° & 2° hemostasis are affected.
o Presentation  Bleeding:
• mucocutaneous, gingival, recurrent epistaxis, ecchymosis,
menorrhagia.
o Lab:
• ↑ Bleeding time & aPTT. MCQ
• ↓ Factor VIII.
o Rx:
• DDAVP  for mild disease  ↑ Release of vW factor.
• Cryoprecipitate = contains Factor 8, vWF, Firbinogen, Factor 13.

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