Hemostasis

complex process that stops bleeding, forms stable clot then breaks down clot.

stays where it's put

travels

• primary hemostasis: (platelet activation, adhesion and aggregation)
• Secondary hemostasis: cascade of enzyme conversions leading to stable clot
• Finbrinolysis: breakdown of fibrin clot, activated simultaneously with hemostasis

• blood vessel injury, vasoconstriction, release of collagen
• circulating platelets adhere to damage and collagen, form plug (Von Willebrand)
• Platelets release chemicals activating blood clotting factors
• cross-linked fibrin clot formed in clotting cascade

• damage to tissue activates
• Factor 7 (tissue thromboplastin)
• Activates Intrinsic pathway

calcium

• tissue thromboplastin
• in extrinsic pathway only.

liver

• activated by extrinsic.  
• damage to blood vessel, wet, anionic surface.  
• Factors 12, 11, 9, 8 (kmart special)

• 10, 5, 2, 1, 8
• activated by both extrinsic and intrinsic
• 10a activates 5a, activates 2 (prothrombin into thrombin), activates 1 (fibrinogen into fibrin), stabilizes clot.  8 turns fibrin into clot, prolongs von willebrand's

prothrombin, thrombin

fibrinogen, fibrin

• fragments of megakaryocytes, makes platelets.  
• 200,000 - 500,000 for most species, 100,000 is thrombocytopenia, <50,000 signs of hemmorrhage
• 30-40% in spleen.  
• Birds and reptiles have nucleated platelets.

precursor to thrombocytes

• forms hemostatic plug
• initiates clotting cascade
• initiates clot retraction
• constrict blood vessels
• phagocytize some particles, particularly damaged cell membrane.

EDTA tube, used to check platelets

citrate.  Used to check clotting factors

used to check fibrin split products

• Checks intrinsic and common (12, 11, 10, 9, 8, 5, 2, 1)
• Dogs: 2-10 minutes
• Cats: 8 minutes
• Horses: 4-15 minutes
• Cattle: 10-15 minutes

• Detect abnormalities in platelet function and von Willebrands
• usually 1-5 minutes.  
• Long indicates thrombocytopenia (usually already know), platelet dysfunction, vWF deficiency

pinpoint bruising on gums/pinna.  Look at CBC, if normal do buccal mucosa bleeding time test

• platelet estimate (peripheral blood smear)
• platelet manual count (hemocytometer, within 5 h)
• Platelet automated count (automated cell counter, trouble with overlap with RBC and clumping)

• examine monolayer in blood smear, count min 10 microscopic fields
• d/c/cw 8-10 platelets per field min
• horse 5 platelets per field min
• each platelet = 15,000-20,000 platelet/uL
• average # x 15,000

• morphology (young are macro, increased production)
• cats have larger platelets
• nonactivated have granules, activated may or may not.

• Evaluates plately number and function in intrinsic and extrinsic.  
• Checks platelet function (don't use if on aspirin)
• depends on interaction between platelet receptors, thrombin, fibrinogen.  
• 1-2 hours for good clot retraction

abnormal platelet function

blotches and bruises on gums, can be pinna as well.  Indicates low platelets.

splenomegaly, hypothermia (liver)

drugs, chemo, infections, irradiation, marrow replacement

• immunologic (IMT)
• non-immunologic (blood loss, DIC, localized intravascular coagulation, vasculitis (leaky vessels), drugs, envenomation, rodenticide)

thrombocytopenia, hemodilution

• usually no clinical signs.  
• iron deficiency anemia (non-regenerative anemia, microcytic, hypochromic)
• inflammatory conditions
• epinephrine release (fear or pain)
• myeloproliferative disorders

• platelets aren't low, just not working.  
• Consider with prolonged bleeding time or clot retraction.  
• Can be hereditary or acquired.  
• drug exposure (NSAIDs, antihistamines, iso, phenylbutazone in horses), envenomation, hepatic disease, increased fibrin degredation products, immune mediated, Infectious (FeLV), renal failure, neoplasia

• measure protein on refractometer (100mg-500mg/dL)
• decreased: liver disease, congenital or factors used up.  Hemolysis and lipemia falsely used up.  
• increased: inflammation, hyperadrenocorticism, pregnancy, nephrotic syndrome in dogs (proteinuria, hypoalbuminemia, hypercholesteralemia, edema)
• DIC: can be any reading of platelets.

• ACT.  Evaluates intrinsic and common (all factors but 7), not very sensitive.  90-95% problem to detect
• Blood into tube with diatomaceous earth, 37 degrees, check for clot time.
• horses<190 sec
• cattle<180 sec
• cats< 75 sec
• dogs<100 sec

• tests intrinsic and common pathways.  
• blue top, 9:1 blood to citrate, centrifuge within 60 minutes, keep refrigerated.  Analyze within 2 hours or freeze.  
• 8-13 sec in dog, <30% normal control.  
• Indicates trouble in factors, substitute known deficiency factors and see if corrects.
• check for liver disease, vitK deficiency, drug overdose, toxins and DIC

• evaluates extrinsic and common.  
• citrate tube (9:1), treat sample like PTT.  
• normal is 6-8 sec in dog, <30% longer than normal control.
• indicates deficiency of factors in extrinsic (7) or common (10, 5, 2,1)
• liver disease
• Rodenticide affects #7 (most common)

• Factor VII deficiency (extrinsic pathway, PT) because it has the shortest half-life.  Eventually all pathways will be effected (2,7,9,10).  
• Early rodenticide = normal PTT, ACT

• Protein Induced (Invoked) by Vitamin K Absence.  Thrombotest.  
• Looks for built-up precurser proteins not used because of vit. K deficiency.  (Pre-2, Pre-7, Pre-9, Pre-10)
• rarely run, not better than PT for rodenticide.  Good for subtle extrinsic/common disorders.

• formed when a clot is degraded, evidence of fibrolysis.  
• Used to find DIC and thromboembolism in all but horses.  
• d-dimer better than FDP for fibrinolysis (not DIC or TE)

• decreased platelets
• normal PT
• normal PTT
• variable ACT
• abnormal clot retraction
• prolonged BMBT.

• most common coagulopathy.  
• Caused by bone marrow damage, infections, immune, abnormal distribution, low production/survival, hemodilution

• normal platelet count
• normal PT
• normal PTT
• normal ACT
• Prolonged BMBT
• abnormal clot retraction.

• abnormal platelet function.  
• Congenital or acquired through drugs (Aspirin), renal failure, increased FDPs (fibrinolysis, DIC), envenomation, hepatic disease, immune, infection, neoplasia.

• normal platelets
• normal PT
• prolonged PTT
• Prolonged ACT

• Hemophilia A
• hemophilia B 
• von Willebrand's Disease

• Most common intrinsic pathway defect.  
• Factor 8 deficiency
• Severe hemorrhage and ecchymoses
• sex-linked recessive--males in any breed

• intrinsic pathway defect
• factor 9 deficiency
• mild to severe bleeding
• sex-linked recessive--males in any dog and DSH cats (siamese)

• Most common hereditary bleeding disorder in dogs (dobermans), rare in others.  
• Missing or ineffective von Willebrand factor, which decreases factor VIII and makes platelets not adhere.

• mild to severe mucosal hemorrhages
• cutaneous bruising
• prolonged hemorrhage from trauma/surgery (tail docking, tooth extraction, dewclaw removal, blood extraction)
• Hemoarthrosis and hematomas in horses

• prolonged BMBT without thrombocytopenia
• normal PT
• normal or mildly prolonged PTT
• von Willebrand antigen test (ELISA) uses anti-vWF antibodies as a % of control.  50% is positive, 70% is negative (between unclassified)

enzyme linked immuno-sorbant assay

• Factor VII deficiency (bruising not bleeding)
• early hepatic disease (eventually more problems)
• early vit K deficiency/antagonism/absense (Warfarin toxicity), will eventually effect all.

• prolonged PT
• prolonged PTT
• prolonged ACT
• normal platelets

• will effect II, VII, IX, X
• effects VII first, shortest half-life
• bleeding is common (can present as breathing problems) 3-7 days after exposure
• Can come from warfarin or rodenticides
• Therapeutic coumadins
• sweet clover or sweet vernal grass (large animals)

• rarely causes hemorrhage
• vitK absorbed in intestine, produced/ingested by intestinal bacteria
• Caused by serious, prolonged anorexia, malabsorption of vitamin K (fat-soluble, so no-fat diet)

• Liver makes I, II, V, VII, VIII, IX, X, XI, XII
• very severe liver disease causes hemorrhage

disseminated intravascular Coagulation

• LOTS of things.  Thromboplastin in tissue exposed, sets off clotting cascade.  
• Septicemia, viremia, parasites, tissue injury, intravascular hemolysis, obstetric complications, malignancy, shock, liver disease, pancreaitis, GDV, abomasal displacement, toxins

• starts as hypercoagulation due to activation of clotting cascades (not evident clinically)
• multiple small clots form in vessels, consuming platelets and clotting factors
• Fibrinolysis, leaving d-dimers and fibrin split products
• fibrin split products (FDPs) are anticoagulants.  
• Severe hemorrhage

• decreased platelets (first sign, prolonged BMBT)
• Prolonged PT
• Prolonged PTT
• Prolonged ACT
• Decreased fibrinogen
• increased FDP or d-dimers