Introduction
- Bleeding disorders are conditions in which the blood does not clot properly, causing excessive or prolonged bleeding.
- Hemostasis is the body’s natural process of stopping bleeding through platelet plug formation, blood clotting, and clot breakdown.
- Bleeding disorders may be inherited (such as hemophilia and von Willebrand disease) or acquired (such as liver disease, vitamin K deficiency, or anticoagulant therapy).
- Common symptoms include easy bruising, nosebleeds, gum bleeding, heavy menstrual bleeding, and prolonged bleeding after injury or surgery.
- Laboratory tests help identify the cause of abnormal bleeding and evaluate the body’s clotting ability.
- Common tests include CBC, platelet count, Prothrombin Time (PT), Activated Partial Thromboplastin Time (aPTT), fibrinogen, and D-dimer.
Physiology of Hemostasis
Hemostasis occurs in three major phases:
1. Primary Hemostasis
- Vasoconstriction
- Platelet adhesion
- Platelet activation
- Platelet aggregation
- Formation of platelet plug
Components
- Blood vessels
- Platelets
- von Willebrand Factor (vWF)
2. Secondary Hemostasis
Activation of coagulation factors leads to fibrin formation.
Coagulation pathways include:
- Intrinsic pathway
- Extrinsic pathway
- Common pathway
The final product is a stable fibrin clot.
3. Fibrinolysis
After tissue repair:
- Plasmin degrades fibrin
- Clot dissolves
- Blood flow returns to normal
Causes of Bleeding Disorders
Inherited Disorders
- Hemophilia A
- Hemophilia B
- von Willebrand Disease
- Rare coagulation factor deficiencies
Acquired Disorders
- Liver disease
- Vitamin K deficiency
- Disseminated Intravascular Coagulation (DIC)
- Anticoagulant therapy
- Massive blood transfusion
- Chronic kidney disease
- Bone marrow disorders
Initial Laboratory Tests
Patients with abnormal bleeding usually undergo first-line investigations:
- Complete Blood Count
- Peripheral Blood Smear
- Platelet Count
- PT
- INR
- aPTT
- Fibrinogen
- D-Dimer
These tests identify the majority of coagulation abnormalities.
1. Complete Blood Count (CBC)
Evaluates:
- Hemoglobin
- Hematocrit
- White Blood Cells
- Platelet Count
Clinical Importance
Low platelet count (Thrombocytopenia) is one of the commonest causes of bleeding.
Normal platelet count: 150,000–450,000/µL
Interpretation
| Platelet Count | Clinical Significance |
|---|---|
| >100,000 | Usually no spontaneous bleeding |
| 50,000–100,000 | Mild bleeding risk |
| 20,000–50,000 | Moderate bleeding |
| <20,000 | Severe spontaneous bleeding |
2. Peripheral Blood Smear
Examines:
- Platelet morphology
- Giant platelets
- Platelet clumping
- Schistocytes
- Blast cells
Useful in:
- TTP
- DIC
- Leukemia
- Bernard-Soulier syndrome
3. Bleeding Time (Historical Test)
Measures platelet plug formation.
Normal: 2–7 minutes
Currently replaced by:
- Platelet Function Analyzer (PFA-100)
- Platelet aggregation tests
4. Platelet Function Tests
Used when platelet count is normal but bleeding persists.
Includes:
- Platelet Function Analyzer (PFA-100/200)
- Platelet Aggregometry
- Flow Cytometry
Useful for diagnosing:
- Aspirin effect
- Glanzmann thrombasthenia
- Bernard-Soulier syndrome
- von Willebrand Disease
5. Prothrombin Time (PT)
Measures:
Extrinsic pathway
Factors assessed:
- I
- II
- V
- VII
- X
Normal Range: 11–14 seconds
Prolonged PT Indicates
- Vitamin K deficiency
- Liver disease
- Warfarin therapy
- Factor VII deficiency
- DIC
6. International Normalized Ratio (INR)
Standardized PT value.
Normal: 0.8–1.2
Warfarin therapy target: 2.0–3.0
Mechanical heart valves: 2.5–3.5
7. Activated Partial Thromboplastin Time (aPTT)
Evaluates:
Intrinsic pathway
Factors:
- VIII
- IX
- XI
- XII
Common pathway factors
Normal Range: 25–35 seconds
Prolonged aPTT
Seen in:
- Hemophilia A
- Hemophilia B
- Lupus anticoagulant
- Heparin therapy
- DIC
8. Thrombin Time (TT)
Measures:
Conversion of fibrinogen into fibrin.
Normal: 14–19 seconds
Increased TT
Occurs in:
- Hypofibrinogenemia
- Dysfibrinogenemia
- Heparin therapy
- DIC
9. Fibrinogen Assay
Normal: 200–400 mg/dL
Low Fibrinogen
Occurs in:
- DIC
- Liver failure
- Massive bleeding
High Fibrinogen
Occurs during:
- Pregnancy
- Infection
- Inflammation
10. D-Dimer Test
Measures fibrin degradation products.
Elevated in:
- DIC
- Venous thromboembolism
- Pulmonary embolism
- Surgery
- Trauma
Not specific for bleeding disorders but valuable in DIC diagnosis.
11. Mixing Studies
Performed when PT or aPTT is prolonged.
Patient plasma is mixed with normal plasma.
Correction
Suggests: Coagulation factor deficiency.
No Correction
Suggests: Presence of inhibitors.
Examples:
- Lupus anticoagulant
- Factor VIII inhibitor
12. Coagulation Factor Assays
Performed when screening tests are abnormal.
Measures activity of:
- Factor VIII
- Factor IX
- Factor XI
- Factor XIII
- Factor VII
- Others
Applications
Diagnosis of:
- Hemophilia A
- Hemophilia B
- Rare factor deficiencies
13. von Willebrand Factor Testing
Includes:
- vWF Antigen
- Ristocetin Cofactor Activity
- Factor VIII activity
- vWF Multimer analysis
Used for diagnosing:
- von Willebrand Disease
14. Platelet Aggregation Studies
Gold standard for inherited platelet function disorders.
Agonists include:
- ADP
- Epinephrine
- Collagen
- Ristocetin
- Arachidonic acid
Diagnoses:
- Glanzmann thrombasthenia
- Bernard-Soulier syndrome
- Storage pool disorders
15. Global Hemostasis Tests
Modern investigations include: Thromboelastography (TEG)
Provides:
- Clot initiation
- Clot strength
- Clot stability
- Fibrinolysis
Widely used in:
- Trauma
- Liver transplantation
- Cardiac surgery
Rotational Thromboelastometry (ROTEM)
Rapid bedside assessment of coagulation.
Useful in:
- Massive transfusion
- Critical care
- Emergency medicine
Interpretation of Common Laboratory Findings
| Disorder | Platelet Count | PT | aPTT | Fibrinogen | D-Dimer |
|---|---|---|---|---|---|
| Hemophilia A | Normal | Normal | ↑ | Normal | Normal |
| Hemophilia B | Normal | Normal | ↑ | Normal | Normal |
| von Willebrand Disease | Normal | Normal | ↑/Normal | Normal | Normal |
| Vitamin K Deficiency | Normal | ↑ | ↑/Normal | Normal | Normal |
| Liver Disease | ↓/Normal | ↑ | ↑ | ↓ | ↑ |
| DIC | ↓ | ↑ | ↑ | ↓ | ↑↑ |
| Thrombocytopenia | ↓ | Normal | Normal | Normal | Normal |
Clinical Applications
These laboratory tests are routinely used in:
- Evaluation of unexplained bleeding
- Pre-operative screening
- Monitoring anticoagulant therapy
- Diagnosis of inherited coagulation disorders
- Liver disease assessment
- Trauma management
- Disseminated intravascular coagulation
- Intensive care medicine
- Hematology clinics
Advantages
- Early diagnosis
- High diagnostic accuracy
- Guides appropriate treatment
- Helps monitor therapy
- Detects inherited disorders
- Prevents unnecessary transfusions
- Improves surgical safety
Limitations
- Some tests require specialized laboratories.
- Platelet function tests are technically demanding.
- Screening tests may be normal in mild bleeding disorders.
- Results can be influenced by medications such as aspirin, clopidogrel, heparin, and warfarin.
- Clinical history and physical examination remain essential for accurate interpretation.