This document discusses the pathophysiology and diagnosis of hemorrhagic disorders in veterinary medicine. It begins by describing the functions of blood components like red blood cells, white blood cells, platelets, and plasma. It then examines various causes of hypoproteinemia and hypofibrinogenemia. The rest of the document details different types of acquired and congenital coagulation defects, platelet disorders, diagnostic tests for bleeding disorders, and potential treatments.

1. Dr. Ajith Y. MVSc PhD
Assistant Professor,
Department of Veterinary Medicine
Faculty of Veterinary and Animal Sciences
Banaras Hindu University

4. • Supplies cells with water, electrolytes, nutrients, and
hormones and removes waste products.
- RBC supply oxygen,
- WBCs protect against foreign organisms
- Platelets initiate coagulation
- Plasma other functions
• Pathophysiology of diseases can be assessed.

6. • Water 94-96% and Solids 4-6%.
• What is diapedesis???

8. A) Hypoproteinemia with hypoAlb and hypoglob:
i. Relative hypoproteinemia: Excessive fluid therapy
ii.Absolute hypoproteinemia: Reduced production,
malnutrition and starvation, hemorrhage, liver disease,
glomerulonephritis, protein losing enteropathy,
Vascular leakage.
B) Hypoproteinemia with hypoAlb and normal glob
Insufficient production of albumin, liver disease,
malnutrition or starvation, Amyloidosis , Chronic
peritonitis or pleuritis, Intestinal parasitism, Renal
disease

9. C) Hypoproteinemia with Normal Alb and hypoglob:
Failure of transfer of passive immunity in neonates,
Immunodeficiency syndromes, decreased production of
gammaglobulins
D) Hypofibrinogenemia: Disseminated Intravascular
Coagulation (DIC).
E) Hyperfibrinogenemia: Acute phase protein, Acute Inflmn
F) Normoproteinemia with hyperglobulinemia (A:G <0.6)
Parasitism, Th2 humoral immunity, chronic inflmn
G) Panhyperproteinemia
Dehydration, Polyuria, Excessive sweat

10. • lethargy, ill-thrift
• Symmetric dependant edema

11. • A:G ratio and Plasma Osmotic Pressure for assesment
• Correction of inciting cause
• Plasma transfusion: Albumin elevation 2.0 g/dL desired
Current Alb = BW(kg) x 0.05 x (Alb conc in g/L)
Desired Alb = BW(kg) x 0.05 x (desired Alb conc in g/L)
Alb required (g) = Desired Alb- Current Alb
Vol plasma required (L) = Alb required (g)/
Alb conc in transfused plasma (g/L)

13. Presence of Hemorrhage of unusual
duration or severity; Either external or
Internal or petechiae or echymosis on
mucosa/serosa/skin.
Occurs due to increased capillary fragility,
disorders in platelet function or defects in
coagulation mechanisms.

14. • Vasculitis
- Septicemic and viremic diseases:
Direct damage to endothelium due to infection.
African Horse Sickness, Equine herpes virus I
Anaplasma phagocytophila, Salmonella, Pasteurella
Evident by petechial and echymotic mucosa clinically
Throughout the body in PM examination
- Purpura hemorrhagica
Immune complex (IgA) mediated endothelial damage
Leukocytoclastic vasculitis
Sequelae of strangles (Streptococcus equi)
- Inflammation can be treated with corticosteroids

15. • COAGULATION DEFECTS (ACQUIRED)
-Intoxications, impair production or function of clotting factors
Protein losing nephropathy- antithrombin-Thrombosis (cattle)
Protein losing enteropathy- antithrombin-Thrombosis (horse)
Vit. K depend. factor deficiency- coumarol/ warfarin poisoning
Vit. K responsive hemorrhagic syndrome in post weaned pigs
Snake venom: Both procoagulants and anticoagulants-Epistaxis
Carcass hemorrhage or blood splash-lambs-Coumarin plant
Electrical stunning also produce carcass hemorrhage
- Depletion of clotting factors: DIC
Fungal toxins: Aflatoxins, Trichotecenes, Rubratoxin
HydroxyEthyl Starch: Prolongs cutaneous bleeding
Umbilical bleeding -newborn piglet: Prevented by Vit C to sows
Fasciola hepatica infestation-sheep: clotting factor deficiency

16. • COAGULATION DEFECTS (CONGENITAL)
- Hemophilia A (Factor VIII:C deficiency)
Foals and sheeps
Sex linked recessive trait (defective gene in ‘X’)
After first few weeks: Hematomas, epistaxis, anemia etc.
- Von Willebrand disease (Factor VIII:vWF deficiency)
vW Factor is a carrier protein for factor VIII
Mediates platelet adhesion to exposed subendothelium
Type I, II & III: Reported in horse, pig, sheep & calves
Autosomal recessive trait linked to ‘X’ chromosome
Desmopressin increase release of vWF from endothelium
- Factor XI deficiency: HF cattle
- Prekallikrein deficiency: Horses-Failure to clot
- Fibrinogen deficiency: Lamb

17. • PLATELET DISORDERS
- Thrombocytopenia- Decreases number
Decreased production: also Neutropenia & anemia
Bracken fern, Trichothecene, Furazolidone poisonings
Radiation injuries and drug side effects
Myeloid dysplasia and bone marrow hypoplasia
Increased destruction: Immune mediated
Inflammation and infection: EIA, Anaplasma, swine fever, BVD
Isoimmune thrombocytopenia: Neonates-colostral antibodies-IgG
Autoimmune thrombocytopenia: Adults-Penicillin
Dexamethasone- 0.040mg/kg IM/IV/PO OD
Prednisolone- 1mg/kg PO
Azathioprine- 0.5-1.5mg/kg PO
Spleenectomy
Increased consumption: Trauma and DIC

18. - Pseudothrombocytopenia
Aggregation of platelets ex-vivo with anticoagulants
Occur in EDTA, Heparin; Not in Trisodium citrate
Clumps of platelet on blood smears
- Thrombocytosis- Increased number
Primary: Excessive megakaryocyte production
Secondary: SIRS & chronic infections in young animals
(Chronic pneumonia, septic arthritis, colitis)
Exercise, Adrenaline, steroids and vincristine
- Thrombasthenia- Reduced function
Uremia, Liver failure, septicemia
Aspirin prevent platelet aggregation-in horse, not in cattle
Dextran inhibit platelet function
Glanzmann’s disease in horse

19. • Demonstration of abnormalities in activity, concentration
or function of components of blood coagulation.
• But, Biopsy required for vasculitis.
• Bleeding time (in vivo): a controlled wound on skin- Time
from wound creation until the bleeding stops. (<5 min)
• Activated clotting time (ex-vivo): Fresh blood in glass
tubes is incubated in water bath (37oC) for 1 min. Checked
for clot formation every 30-60 min.

20. • For estimation of clotting factors
- Chromogenic assays and ELISA
• Markers of Fibrinolysis and DIC
- Fibrin Degradation Products (FDP) - Poor sensitivity (<40%).
- D-dimer (a FDP) – Sensitivity (50%) and specificity (97%).
• Marker of anticoagulant activity
- Antithrombin: co-factor of heparin
• Platelet count: Abnormal <1 lakhs; Hemorrhage < 40,000

21. • Reticulated platelets: Thiazole orange dye- Normal (1-3.4%)
- Bone marrow regenerative response

23. • Clot retraction time: Blood in a glass tube at 37oC-
Measure of platelet function- Maximum clot retraction
occurs by 1-2 hours.
• Prothrombin time: Extrinsic clotting system activity –
Tissue factor
• Activated partial thromboplastin time: Intrinsic
clotting system function – kaolin and calcium
• Thrombin time: Common pathway – Bovine thrombin
• Highly variable

24. • Serum sample is minimally useful in tests for clotting
factors.
• Ideal anticoagulant: Trisodium citrate (1 part 3.8%
trisodium citrate in 9 parts of blood) – Ca chelation
• Not suitable anticoagulants
- Heparin: Inhibit thrombin activity, activate platelets
- EDTA: Interferes with platelet function
• Pseudothrombocytopenia: due to anticoagulant induced
ex-vivo aggregation of platelets.

25. • Plasma (2-10ml/kg) can be used to replace clotting
factor deficiency either due to failure in production or
increased consumption or dilution.
• Fresh frozen kept at -80oC retain much of clotting factors
• Platelet rich plasma can be prepared by centrifugation of
blood at 150xg (1000-1200 rpm) for 20-30 min.
• Aminocaproic acid: 30-100mg/kg IV, Inhibits
fibrinolysis, inhibit bleeding by persisting clot
• Tranexamic acid: Inhibits fibrin degradation
• Carbazochrome: Stabilizes capillary membrane
• Formalin: Horse (1L of 0.37-0.74% formalin in RL)
Goats (5.5% formalin in RL)

26. • Aspirin: In horses (12mg/kg), inhibit platelet aggregation;
whereas, not in cattle at 100mg/kg.
• Warfarin: Reduces concentration of Vit. K dependent
clotting factors by inhibiting hepatic production.
• Heparin and dalteparin/enoxaparin: 40IU/kg IV every
12-24 hrs
• Sodium pentosan polysulfate: Treatment of arthritis
• Hirudin: Anticoagulant from leaches. Thrombin inhibitor
• Tissue plasminogen activator: Dissolution of clots
• Streptokinase or Urokinase: Dissolution of fibrin clots