Hemostasis and Coagulation

• Hemostasis is the process that stops bleeding after a blood vessel injury, involving vasoconstriction, platelet plug formation, and blood clotting to seal the wound, ensuring vascular integrity and preventing excessive blood loss.
• Normal hemostasis requires blood vessels to constrict, platelets to adhere and aggregate, clotting factors to activate and form a fibrin clot, endothelial cells to regulate clotting, and calcium with other cofactors for activation and stability.
• Hemostasis involves:
  • Vasoconstriction
  • Platelet activation
  • Coagulation cascade
  • Clot breakdown.
• A platelet plug differs from a clot, with the former forming in primary hemostasis and the latter in secondary hemostasis.

Step 1: Vasoconstriction

• Injured arteries constrict to decrease blood loss rate and cause turbulence, which facilitates platelet attachment.
• Damage to the vascular lining and exposure of compounds stimulate the overall hemostasis process.

Step 2: Platelet Response

• Damaged vessels expose the subendothelial basement membrane, causing platelet activation.
• Activated platelets release chemicals like vWF, marking the end of primary hemostasis.

Step 3: Coagulation Cascade

• Clotting factors remain inactive until activated by calcium and vitamin K, to convert FIBROGEN to FIBRIN.
• The intrinsic and extrinsic pathways are parts of the coagulation cascade and are also called PT and PTT.
• Factor 1 is firbriogen (The goal), Factor 2 is prothrobim, Factor 3 is tissue factor
• Factors II, VII, IX, and X require vitamin K.
• Most factors need calcium.
• Each activated factor stimulates the next step and is rapidly destroyed by local enzymes, localizing coagulation.
• Clotting factors are present in plasma in inactive forms and are activated by a precursor
• The intrinsic pathway is done by a precursor being active ex factor 11 needs factor 12 factor an so on.
• The extrinsic pathway is activated secondarily to external trauma and release of tissue factor

Step 4: Clot Breakdown (Fibrinolysis)

• Plasminogen converts to plasmin, breaking down fibrin into fibrin degradation products (FDPs).

Clinical Signs of Hemostatic Disorders

• Primary disorders are characterized by petechiae which are very common, rare hematomas, bleeding at multiple sites involving mucous membranes, and prolonged bleeding time from cuts.
• Secondary disorders manifest as rare petechiae, common hematomas, localized bleeding, bleeding in muscles and joints, and recurrent bleeding from the same sites.

Von Willebrand Factors

• vWF enables platelets to become "sticky".
• Factor VIII is bound to vWF when inactive.

Tests for Hemostasis

• Primary hemostasis tests include platelet counts, BMBT (Buccal mucosal bleeding time), and VWF
• Secondary hemostasis tests include ACT (activated clotting time), PT (tests extrinsic hemostasis), PTT (tests intrinsic hemostasis), and fibrinogen assays.
• Tertiary hemostasis tests assess fibrinogen degradation products.

Acquired and Inherited Disorders of Hemostasis

• Acquired disorders can occur at any age and may involve toxicities, drug reactions, or secondary complications from infections, disease, and neoplasia.
• Inherited disorders often present in young animals and may affect littermates, with history and breed predisposition being important factors.

Primary Disorders of Hemostasis

• Acquired disorders:
  • DIC (impairs platelet function)
  • Drug reactions (aspirin)
  • Thrombocytopenia
  • Disorders of platelet production
• Inherited disorders:
  • Von Willebrand disease
  • Basenji hound thrombopathy
  • Thrombopathias (failure of platelet aggregation)

Secondary Disorders of Hemostasis

• Acquired disorders:
  • Toxicities
  • Infections
  • Liver disease
  • DIC
• The most common:
  • Inherited: vW DISEASE
  • Acquired: THROMBOCYTOPENIA

Von Willebrand's Disease (vWD)

• vWD is a congenital/inherited defect causing platelet dysfunction due to a deficiency of plasma vWF.
• vWD is characterized by a deficiency of von Willebrand factor (vWF), a plasma protein that aids platelet adhesion to the vessel wall during primary hemostatic plug formation.
• vWD can result in abnormal primary hemostasis (platelet plug formation) and prolonged bleeding time.
• VWD is common in corgis, Dobermans, and German Shepherds.
• In animals with vWD, bleeding commonly involves mucosal surfaces and is observed after trauma or surgery.
• Clinical signs may include:
  • Epistaxis (nose bleed)
  • Gingiva bleeding
  • Hematuria
  • Excessive vaginal hemorrhage
  • GI bleeding
  • Multiple small bruises
  • Purpura
  • Spontaneous bleeding from mucosal surfaces
  • Excessive bleeding from tooth extractions
  • Prolonged bleeding from wounds
  • Increased cutaneous bleeding after venipuncture
• Presumptive diagnosis:
  • Platelet count and morphology are generally normal with normal PT and PTT
  • Prolonged BMBT is suggestive of vWD.
  • The BMBT measures the time required for platelets to plug a small laceration in blood vessels.
  • BMBT isn't prolonged with deficiency of coagulation factors, but is prolonged in vWD due to abnormal platelet function.
• Definitive diagnosis is achieved by antigenic measurement or testing for vWF antibodies (ELISA based immunological test).
• The sample for the vWF antigen test is citrated plasma.

Rodenticide Toxicity

• Coagulopathy is caused by reduced vitamin K dependent clotting factors due to exposure to anticoagulant rodenticides.
• Anticoagulant rodenticides inhibit an enzyme responsible for recycling of vitamin K, reducing production of vitamin K dependent coagulation factors.
• Signs/Clinical presentation:
  • History of roaming
  • Lethargy
  • Epistaxis
  • Melena
  • Bruising
  • Blindness
  • Seizures
  • Dyspnea
• Physical exam findings may include:
  • Depression
  • Pallor
  • Hematemesis
  • Hematuria
  • Gingival bleeding
  • Prolonged bleeding from wounds/venipuncture sites
  • Hematomas
  • Hemorrhage into body cavities.
• Risk factors:
  • Small doses over several days
  • Different "generations" of rodenticides (warfarin, brodifacoum, bromadiolone, indandiones), with increasing toxicity.
• Diagnostic Procedures:
  • Evaluation of PCV, TP, CBC, platelets, and coagulation profile
  • Prolonged ACT, PT, and PTT.
  • Biochemistry profile
  • Urinalysis
• Treatment includes:
  • Finding the source of exposure
  • Induction of emesis if known
  • Recent ingestion
  • Activated charcoal
  • Gastric lavage
  • Vitamin K (antidote)
  • Restricted activity
  • Monitoring
  • Follow-up treatment and bloodwork.

DIC (Disseminated Intravascular Coagulation)

• DIC is a secondary condition resulting from another disease or condition.
• DIC involves concurrent activation of coagulation and fibrinolytic systems, potentially leading to consumption of coagulation factors, fibrinogen/fibrin, and platelets resulting in bleeding/hemorrhage.
• If clot formation exceeds lysis, fibrin may accumulate in microvasculature, resulting in ischemia and organ failure.
• DIC is due to systemic activation of coagulation and fibrinolysis.
• DIC can be triggered: vascular stasis or endothelial injury, generalized/systemic infections, neoplasia, severe tissue damage, or shock.
• Conditions:
  • Heat stroke
  • Sepsis
  • Viremia
  • Pancreatitis
  • Neoplasia
  • Parasitic infections
  • Intravascular hemolysis
  • Immune-mediated diseases
  • Exposure to venom/toxins
  • Massive tissue injury
  • Obstetric complications
  • Insufficiency of major organs
  • Diabetes mellitus
  • Acidosis
  • Polycythemia
  • Severe prolonged hypotension
  • Severe volume depletion
  • Impaired blood flow to a major organ
• Hematological findings consistent with DIC:
  • Thrombocytopenia
  • Prolonged PT and PTT
  • Hypofibrinogenemia
  • Fragmentation of RBCs (schistocyte formation)
  • Increased FDPs (fibrin degradation products)
• Treatment:
  • Manages underlying conditions
  • Administers of anticoagulants
  • Fluid and transfusion therapy
• Prognosis:
  • guarded prognosis