This document discusses bleeding disorders and their evaluation. It notes that bleeding disorders like hemophilia A and von Willebrand disease are common. A proper evaluation of a bleeding patient requires assessing whether the bleed is congenital or acquired, where the bleed is located, and other relevant clinical details. Laboratory tests that are part of the evaluation include complete blood count, prothrombin time, activated partial thromboplastin time, and specific coagulation factor assays. The document provides details on how these tests are performed and interpreted to diagnose specific coagulation factor deficiencies or other bleeding disorders.

1. Dr. Sourabh Mandwariya
Pathologist & Nodal Officer Central Lab,
Indira Gandhi District Hospital, Mandsaur

2.  Bleeding disorders are very common
 Haemophilia A & vWD most common
 Bleeding patient can be a nightmare
 Proper evaluation & anticipation is needed

3.  Normal physiological mechanism for keeping
the blood in fluid state in vascular system
and for prevention of hemorrhage by
complex interaction of blood vessel walls,
platelets and plasma proteins.
 Primary Hemostasis (Platelet plug formation)
 Secondary Hemostasis (Stable fibrin clot)

4.  Three main components
 Blood Vessel Wall
 Constriction of blood vessel
 Endothelial cell –
 von Willebrand factor (vWF)
 Tissue Factor
 Platelet activating factor

5.  Life span – 7 to 10 days
 Function
 Adhesion
 Release Reaction (ADP, TxA2, Serotonin)
 Aggregation

7.  Coagulation Factors
 Coagulation Inhibitors
 Fibrinolytic Systems

8.  Coagulation Factors
I. Fibrinogen
II. Prothrombin
III. Tissue Factor, Thromboplastin
IV. Calcium
V. Labile Factor
VI. No Factor
VII. Stable Factor
VIII. Antihemophilic globulin; Antihemophilic factor
IX. Christmas Factor
X. Stuart-Prower Factor
XI. Plasma Thromboplastin Antecedent
XII. Hageman Factor
XIII. Fibrin Stabilizing Factor; Laki-Lorand Factor
Prekallikrein –Fletcher Factor
High Molecular Weight Kininogen – Fitzgerald Factor

9.  Coagulation Factors
 Three Groups
1. Fibrinogen Group: I, V, VIII, XIII
2. Vitamin-K Dependent: II, VII, IX, X
3. Contact Group: XI, XII, HMWK, Prekallikrein

10.  Extrinsic Pathway
 Intrinsic Pathway
 Common Pathway

12.  Coagulation Inhibitors

13.  Fibrinolytic System

16.  Inherited Disorder of Coagulation
 Hemophilia A (Classical Hemophilia, F VIII
Deficiency)
 Point Mutation or deletions of F VIII gene (Long arm of
the X chromosome)
 X-linked recessive disorder
 Primarily affecting males; females are carriers but do
not manifest the disease.
 Incidence – 1:10000

17.  Inherited Disorder of Coagulation
 Hemophilia A (Classical Hemophilia, F VIII Deficiency)
 Three Types
 Mild - > 5%(Excess Bleeding only after major trauma or
surgery)
 Moderate – 1-5%(Excess Bleeding after mild to
moderate trauma; occasional hemarthrosis;
spontaneous bleeding infrequent)
 Severe - < 1% (Frequent and spontaneous deep tissue
hematomas, Hemarthroses, Intracranial hematomas, )

18.  , Hemarthroses

21.  Acquired Inhibitors of Coagulation
1. Specific
 Against F VIII (Multi transfused patient, Old Age, RA,
Postpartum females)
2. Non-specific
 SLE, Neoplasia, HIV

22.  Is it a congenital or acquired bleeding
If congenital - Factor defi / Platelet / vWD
If Acquired - Surgical / Coagulopathy / Drugs
 Is bleed present at presentation
 Special situations - On drugs / Pregnancy /
Neonate
 Other Organ Involvement

23.  Clinical Evaluation
 Easy Bruising
 Spontaneous Bleeding
 Multiple Sites Bleeding
 Repeated Episodes of Excessive Bleeding
 Restart of bleeding hours or days following injury
 Similar past or family history
 Poor wound healing
 Bleeding is out of proportion to the degree of trauma.

24.  Clinical Evaluation
 Petechia - ≤2 mm in diameter
 Purpura - ≥3 mm but <1 cm in diameter
Both in Primary Hemostatic disorder
 Ecchymosis (Bruise) - >1 cm in diameter
(Defective hemostasis or trauma)
 Hematoma – Large area of hemorrhage
(Coagulation Disorder)
 Hemarthrosis – Coagulation Disorder Specially –
Hemophilia.

25.  Clinical Evaluation
 Muco-cutaneous bleeding (Purpiura, Petechia, Gums Bleeding,
Epistaxis, GI Bleeding, Menorrhagia)- Platelet Disorders, vWD
 Cephalhematomas, hemarthrosis, Intramuscular Hematoma, Intra
Cranial Bleeding, Retroperitoneal Haemorrhages – Hemophilia,
Afibrogenemia, vWD
 Umblical Stump Bleeding – Afibrogenemia, F XIII Defecicency
 Defective wound healing – F XIII Defeciency
 Recurrent Sever Epistaxis – Hereditary hemorrhagic Telangietasia

26.  Clinical and Laboratory
evaluation both are
necessary.
 Detailed Family History
 Family Tree

27.  Clinical Evaluation
 History of bleeding only in males and positive
family history on maternal side – X linked
Disorders (F VIII & F IX deficiency)
 Autosomal Recessive Disorders – Both males and
females are affected, History of consanguinity)
 Autosomal Dominant Disorders – Both sex, Older
generation, in one parent.

29.  Laboratory Evaluation
 CBC
 Peripheral Smear
 Bleeding time
 Clotting Time
 Prothrombin Time
 Activated Partial Thromboplastin Time

30.  Prothrombin Time (PT)
 Extrinsic (F VII) and Common (F X, F V,
Prothrombin & Fibrinogen)

31.  Prothrombin Time (PT)
 Sample Collection
 Should not use Glass Syrynge
 Trisodium Citrate (3.2%) Anticoagulant (1:9)
 Mix by gentle inversion 5 times
 Centrifuged 3000 RPM for 20 minutes
 Within 02 hrs of Blood collection test should be carried
out

32.  Prothrombin Time (PT)
 Method
 100 µl plasma + 100 µl Thromboplastin Reagent (TF
and Phospholipids)
 Incubate 37ºC for 1 minute
 Add 100 µl Calcium Chloride
 Record time for clot formation
Normal Range – 11 to 16 Seconds

33.  Prothrombin Time (PT)
 Prolongation of PT
1. Oral Anticoagulants
2. Liver Disease
3. Vit K Deficiency
4. DIC
5. Inherited Deficiency of factors of extrinsic and
common pathway

34.  Activated Partial Thromboplastin Time (aPTT)
 Intrinsic (F XII, F XI, HMWK, Prekallikrein, F IX &
F VIII) and Common Pathway

36.  Activated Partial Thromboplastin Time (aPTT)
 Method
 Phospholipid Reagent and Calcium chloride solution in
glass tube at 37ºC
 100 µl plasma and 100 µl Kaloin Solution at 37ºC for 10
minutes
 Add 200 µl Phospholipid and Calcium Chloride Mix.
Note the clotting time.
Normal Range – 30-40 seconds

37.  Activated Partial Thromboplastin Time (aPTT)
 Prolongation of aPTT
1. Hemophilia A or B – Always perform PT along
with aPTT
2. Monitor Heparin Therapy (Activate
Antithrombin III)
3. Inhibitors of Coagulations

38.  Mixing Studies (For distinguish between factor
deficiency and factor Inhibitors)

39.  Interpretation of screening test
1. Only Thrombocytopenia
 Hematological Disease
2. Selective Prolongation of Bleeding Time
 Platelet Function Disorder
 vWD
 Vascular Disorder
3. Selective Prolongation of aPTT
 Intrinsic Pathway
 Heparin Therapy
 Inhibitors
4. Prolongation of aPTT and Bleeding Time
 vWD

40.  Interpretation of Screening Test
5. Selective prolongation of PT
 F VII Deficiency
 Early Vit K Deficiency
 Oral Anticoagulant
6. Prolongation of both PT and aPTT
 Common Pathway Factors Deficiency
 Dysfibrinogenemia
 Liver Disease
7. All Screening test abnormal
 DIC
8. All screening test normal
 Mild form of vWD
 Platelet Function Defect
 Vascular Disorder
 Mild Coagulation Factor Deficency

41.  Specific Test for Hemostasis
1. Factor VIII assay (Normal 50-150%)
 log/log Graph
2. Platelet Aggregation Studies
3. Detection of Fibrinogen/fibrin degradation product
4. Detection of D-dimers
5. Estimation of fibrinogen
6. Platelet Glycoprotein analysis

42.  Specific Test for Hemostasis
 Normal Graph Paper

43.  Specific Test for Hemostasis
 log/log Graph

44.  Mild Congenital disorders can present late in life
 Every bleed in Pediatric age group is not Cong
 Combinations are possible
 History / General examination / Routine Inv
 Specialized investigations needed
 Repeat testing may be needed
 Obstetric bleeding to be tackled very aggressively
 Neonatal evaluation can be tricky

45.  Thank You