What are the basic steps of hemostasis?
- 1. Primary hemostasis- platelet plug
- 2. Secondary hemostasis- fibrin mesh
- 3. Fibrinolysis- removal of the clot
- 4. Neoangiogenesis- formation of a new vessel
Describe how platelet adhesion occurs.
- vonWillibrand Factor released from endothelial cells and binds to collagen in the subendothelial matrix
- vWF binds to platelet receptors, causing them to adhere to the vessel wall
For platelet activation to occur, they must undergo _____________; factors involved in this process include... (5)
conformational changes; Thrombin, ADP, collagen, thromboxane A2, platelet-activation factor
After platelet activation, ___________ occurs to release __________.
platelet degranulation; internal granules ("sticky glove" analogy)
__________ is the most potent platelet activator.
Describe the fibrinolysis step of hemostasis.
- breakdown of mature clot that starts as soon as the clot forms
- results in the formation of FDPs/ D-Dimers
What drives fibrinolysis?
plasminogen is activated by tissue plasminogen activator (tPA)--> plasmin
*********At what stage of the coag cascade does Protein C prevent coagulation?
Protein C blocks Factors VIII and V
********At what stage of the coag cascade does TFPI prevent coagulation?
prevents tissue factor (TF) from being activated to move to factor VII
*******(At what stage of the coag cascade does antithrombin + heparin prevent coagulation?
antagonizes factors X and II
Thrombosis is treated using a(n) ___________.
fibrinolytic agent ("clot buster")
Hyperfibrinolysis is ______________ and must be address with a(n) _____________.
too much clot break down; antifibrinolytic agent ("clot stabilizer")
What are clinical signs of primary hemostatic disorders? (7)
- mucosal bleeding- petechia, ecchymosis, epistaxis, GI hemorrhage, gingival bleeding
- blood loss/ anemia- pale MMs, signs of anemia (tachycardia, tachypnea)
What are clinical signs of secondary hemostatic disorders?
- cavitary bleeding- pleural space, pulmonary parenchyma, abdominal cavity, joints (signs depend on site)
- dyspnea, coughing
- neurologic signs
- blood loss and shock
What tests evaluate primary hemostasis? (4)
- platelet number
- platelet function- BMBT, vWF, PFA
What tests evaluate secondary hemostasis? (4)
- Lee-White CT (glass tube test)
What are normal values for the BMBT?
- dogs <4 minutes
- cats <3 minutes
- [remember: there's no point in measuring BMBT is platelet numbers are decreased!]
What is (OS)PT evaluating?
[Prothrombin time] measures the extrinsic and common pathways
What is aPTT evaluating?
[activated Partial Thromboplastin Time] measures the intrinsic and common pathways
What is ACT evaluating?
[Activated Clotting Time] measures the intrinsic and common pathways, but is less sensitive than aPTT
What are your rule outs for primary hemostatic disorders? (7)
- [thrombocytopenia] destruction of platelets, consumption of platelets, decreased production of platelets, sequestration of platelets
- vWF deficiency
- [thrombocytopathy] renal failure, medications (Hetastarch, Aspirin,Plavix)
What are rule outs for secondary hemostatic disorders? (5)
- inherited factor deficiencies (Hemophilia A- VIII, Hemophilia B (IX)
- liver disease (decreased factor production)
- anticoagulant rodenticide (Vit K antagonism)
- traumatic coagulopathy (loss of clotting factors, hypothermia)
What factors require Vit K for normal function? (4)
II, VII, IX, X
What is the treatment plan for primary hemostatic disorders? (3)
- address underlying cause if possible
- blood products- whole blood, platelet rich plasma
- enhance platelet function- cryoprecipitate, DDAVP
How does cryoprecipitate work?
it's a concentration of vWF and factor VIII
What is DDAVP/ how does it work?
stimulates release of vWF and factor VIII into circulation; it helps with any type of thrmbocytopathy
How are vWF and factor VIII related to one another?
vWF is bound to factor VIII in circulation; when vWF is activated by thrombin, factor VIII is released and rapidly degrades
What is the treatment plan for secondary hemostatic disorders? (2)
- treat primary cause: find/ treat primary cause of DIC, Vit K supplementation, liver disease, etc
- transfusion therapy [if prolonged clotting times AND evidence of ongoing bleeding]
What are the doses for fresh whole blood transfusions?
- K9/EQ/BV: 20-30mL/ kg
- FE: 10-15mL/ kg
What are the doses for fresh frozen plasma and frozen plasma?
- K9/EQ/BV: 10-15mL/ kg
- FE: 5-7.5mL/kg
What are the consequences of thrombosis?
- Microthrombosis--> DIC
- Macrothrombosis--> saddle thrombus, DIC, CATE, AIT, PTE, etc
Thrombosis is secondary to...
- disruption of virchow's triad
- venous stasis, vessel injury, hypercoaguable state
How does SIRS lead to DIC?
- hypercoagulation, blood stasis from vasodilation, endothelial damage (direct or indirect)
- inflammation and coagulation are linked!!!
- DIC is MODS for the hemostatic organ
Describe the diagnosis of DIC. (5)
- presence of disease-causing DIC= SIRS/ sepsis: heat stroke, IMHA, pancreatitis, neoplasia
- depletion of endogenous anticoagulant: low antithrombin
- depletion of clotting factors and/or platelets: low platelet count, low fibrinogen, prolonged PT/aPTT
- evidence of fibrinolysis: increased D-dimers, FDPs
- CBC/ biochem panel: schistocytes, evidence of organ failure
Clotting times may be normal with DIC if you catch it during...
the hypercoaguable phase [Pt/aPTT will be prolonged during the hypocoaguable phase]
What lab abnormalities will you see during the hypercoaguable phase of DIC? (4)
increased D-dimers, decreased platelet count, schistocytes, evidence of thrombosis or organ dysfunction
What lab abnormalities will you see during the hypocaguable phase of DIC? (3)
prolonged PT/aPTT, decreased platelets, clinical bleeding
What is the treatment plan for DIC?
- treat underlying cause
- plasma products ONLY if bleeding (hypocoaguable phase)
- anticoagulant ONLY if hypercoaguable phase
Describe the coagulation cascade.
What are indications for using anticoagulants? (3)
- excessive clot formation
- hypercoaguable DIC
- thromboembolic disease
What drugs are platelet inhibitors? (2)
- plavix (Clopidogrel)
What drugs are coagulation factor inhibitors? (2)
- heparin (unfractionated vs low molecular weight)
Heparin requires sufficient __________ in order to be effective; indications for use of heparin include.. (2)
- antithrombin levels
- prevention of DIC in high risk patients
- clot already present, ex. FATE
Contrast unfractionated heparins versus low molecular weight heparins.
- Unfractionated: varying sized molecules, inactivate multiple factors, unpredictable pharmacology, monitor using aPTT, dose 75-300units/kg
- Low molecular weight: more uniform size, only inactivates factor Xa, more predictable effect, does not affect PT/aPTT (difficult to monitor), Dose 1mg/kg
DIC is ALWAYS...
secondary to another disease!!!