Bleeding disorders result from abnormalities in platelets, coagulation factors, or vessel walls that lead to excessive bleeding. They can be quantitative (↓ platelet count) or qualitative (defective platelet function).
1. PLATELET DISORDERS
Immune Thrombocytopenic Purpura (ITP)
Definition: An immune-mediated destruction of platelets due to IgG antibodies against platelet surface antigens (GPIIb/IIIa, GPIb/IX).
| Feature | Details |
|---|---|
| Mechanism | Type II hypersensitivity; IgG-coated platelets are destroyed in the spleen by macrophages |
| Forms | • Acute ITP: Children, post-viral, self-limited • Chronic ITP: Women, may be the first sign of SLE |
| Clinical Features | Petechiae, purpura, menorrhagia, nosebleeds |
| Lab Findings | ↓ Platelets, ↑ Bleeding time, Normal PT/PTT, Megakaryocytes in bone marrow |
| Treatment | Corticosteroids, IV immunoglobulin, Splenectomy |
Thrombotic Thrombocytopenic Purpura (TTP)
Definition: A disorder due to a deficiency of the ADAMTS13 enzyme, causing large vWF multimers and platelet microthrombi formation.
| Feature | Details |
|---|---|
| Mechanism | Deficiency of ADAMTS13 → uncleaved vWF multimers → platelet aggregation → microthrombi |
| Clinical Features | Pentad: Thrombocytopenia, Microangiopathic hemolytic anemia, Renal failure, Neurologic symptoms, Fever |
| Lab Findings | ↓ Platelets, Normal PT/PTT, Schistocytes, Reticulocytosis |
| Treatment | Plasma exchange (removes antibodies, replaces enzyme) |
Hemolytic Uremic Syndrome (HUS)
Definition: Microangiopathic hemolytic anemia due to endothelial damage, commonly following E. coli O157:H7 infection.
| Feature | Details |
|---|---|
| Population | Children after gastroenteritis (bloody diarrhea) |
| Pathogenesis | Shiga toxin damages renal endothelium → fibrin thrombi in glomeruli |
| Clinical Features | Abdominal pain, Diarrhea, Hemolytic anemia, Thrombocytopenia, Renal failure |
| Treatment | Supportive: fluids, dialysis, RBC transfusions; plasma exchange for atypical cases |
Other Platelet Function Disorders
| Disorder | Defect | Key Point |
|---|---|---|
| Glanzmann Thrombasthenia | Defective GPIIb/IIIa | Impaired platelet aggregation |
| Bernard-Soulier Syndrome | Defective GPIb | Impaired platelet adhesion, large platelets |
| von Willebrand Disease | ↓ or defective vWF | Autosomal dominant, mucosal bleeding, prolonged BT/PTT |
| Drug-Induced | Aspirin, NSAIDs | Inhibits platelet function |
2. COAGULATION FACTOR DISORDERS
| Disorder | Inheritance / Cause | Deficiency | Lab Findings | Treatment |
|---|---|---|---|---|
| Hemophilia A | X-linked recessive | Factor VIII | Normal BT, ↑ PTT | Factor VIII concentrate |
| Hemophilia B (Christmas Disease) | X-linked recessive | Factor IX | Same as A | Recombinant factor IX |
| Vitamin K Deficiency | Acquired | ↓ II, VII, IX, X, Protein C/S | ↑ PT, ↑ PTT | Vitamin K |
| Liver Disease | Acquired | ↓ all clotting factors | ↑ PT/PTT, ↓ fibrinogen | Treat the underlying cause |
3. DISSEMINATED INTRAVASCULAR COAGULATION (DIC)
Definition: Secondary to another disorder causing widespread clotting and bleeding due to the consumption of platelets and coagulation factors.
Common Causes:
- Obstetric complications (placental tissue factor)
- Gram-negative sepsis (TNF activation)
- AML-M3 (promyelocytic leukemia)
- Adenocarcinoma (mucin activation)
- Severe infections (meningococcus, rickettsiae)
Lab Findings:
- ↓ Platelets,
- ↑ PT/PTT,
- ↓ Fibrinogen,
- ↑ D-dimers
Clinical Features: Microthrombi, organ ischemia, bleeding from multiple sites.
Table: Common Platelet Disorders (Summary)
| Mechanism | Examples |
|---|---|
| ↓ Production | Aplastic anemia, Tumor infiltration |
| ↑ Destruction | ITP, TTP, DIC, Hypersplenism |
| Qualitative Defects | vWD, Glanzmann, Bernard-Soulier, Drugs, Uremia |
Key Points to Remember
- ITP: IgG-mediated platelet destruction (Type II HS)
- TTP: ADAMTS13 deficiency → vWF multimers → microthrombi
- HUS: Shiga toxin → endothelial injury → renal failure
- Hemophilia A/B: X-linked, prolonged PTT
- vWD: Most common inherited bleeding disorder, mucosal bleeding
- DIC: Always secondary — think obstetric, sepsis, leukemia
Learning Objective
By the end of this session, medical students should be able to:
Differentiate between major causes of bleeding disorders (platelet, coagulation, endothelial), recognize their pathophysiology, laboratory findings, and clinical features, and outline appropriate management approaches.
