Hemostasis Flashcards
What are the non-enzymatic coagulation factors?
Tissue Factor (III)
Factor Va
Factor VIIIa
Calcium and PLTs
What binds and activates Prothrombin (II) to make Thrombin (IIa)?
Factor Xa
What binds and activates Fibrinogen (I) to make Fibrin (Ia)?
Thrombin (IIa)
The part of secondary hemostasis involving activation of Factor X, Prothrombin to Thrombin, and Fibrinogen to Fibrin is know as:
The common pathway
What are the 3 phases of Cell Based coagulation model?
Initiation
Amplification
Propagation
This is the activator of coagulation in vivo. It is expressed on cells outside the vasculature, and is exposed when the endothelium is disrupted.
Tissue Factor (III)
What binds the circulating Factor VIII:vWF complex, causing the release of vWF and activation of VIII to VIIIa?
Thrombin (IIa)
What is the primary amplifier in primary and secondary hemostasis?
Thrombin
During propagation, large amounts of ______ are produced, and a clot begins to form.
Fibrin
Fibrin is originally produced in a soluble form, but becomes cross-linked with the help of ____ to complete the clot.
Factor XIII
Tissue Plasminogen Factor (TPA) is continually secreted by endothelial cells. TPA and Plasminogen bind to Fibrin, where TPA cleaves Plasminogen, forming _____.
Plasmin
What is the function of Plasmin?
Break down Fibrin strands
The breakdown of Fibrinogen and Soluble Fibrin by Plasmin leads to what by-products?
Fibrin Degradation Products (FDPs)
The breakdown of cross-linked Fibrin by Plasminogen leads to what by-products?
D-dimers
What can measuring D-dimers and FDPs tell us?
How many clots are being formed and broken down.
*DIC!
_______ is involved in fibrinolysis, while ______ inhibits coagulation.
Plasmin; Antithrombin
How does antithrombin inhibit coagulation?
Inhibits Factor Xa and Thrombin
*Without Thrombin, Fibrinogen can’t be activated to form Fibrin.
What protein in circulation binds to antithrombin to express its thrombin binding site and increasing its activity by 1000x?
Heparin
After heparin is released from antithrombin, AT is able to bind with thrombin and form the ___ ______, which is removed from circulation by phagocytes.
TAT complex
What type of coagulation would you expect in a patient with protein-losing nephropathy?
Hyper coagulation!
*Antithrombin is REALLY small, so it’s one of the first molecules to leak out with glomerular injury.
What are the 2 good tests we like to use to measure coagulation activity?
PTT (activated partial thromboplastin time)
PT (prothrombin time)
What anticoagulation factors can we measure to determine fibrinolytic activity?
FDPs
D-dimers
What anticoagulation factor can we measure to determine inhibitor consumption?
Antithrombin (AT) level
What tube is blood collected in for coagulation panels?
Sodium citrate tube (blue top)
Sodium citrate tubes are centrifuged to leave plasma and remove RBCs, WBCs, PLTs and Ca++. How do we determine coagulation function from the plasma?
Add back Ca++ and PLTs in controlled volumes
You are performing an activated partial thromboplastin time (aPTT) test on a dog. You add contact activator, calcium and PLT substitute to your citrated plasma and determine that the coagulation time is prolonged. What is the minimum deficiency of coagulation factors in this dog and which factors are affected?
There is at least a 70% deficiency in factors in order for the aPTT to be prolonged.
Affected factors will be from the intrinsic pathway or the common pathway (XII, XI, IX, VIII ; X, V, II I)
The Activated Clotting Time test (ACT) is inexpensive and uses whole blood + contact activator to measure fibrin clot formation. Although it is an easy way to test the intrinsic and common pathways, why isn’t it commonly used?
Requires a 95% deficiency in factors to be detected as prolonged.
You are performing a prothrombin time (PT) test on a dog. You add tissue factor, Ca++, and PLT substitute to your citrated plasma and determine that the clotting time is prolonged. What deficiencies can this indicate?
Prolonged PT can indicate 70% deficiency in Factor VII (extrinsic pathway) or X, V, II, I (common pathway)
It can also be a good test for Vit K deficiency since Factor VII is Vit K dependent.
Measurement of FDPs and D-dimers is done by immunologic methods, using _______ to identify fibrin fragments and D-dimer antigens.
Antibodies
What can increased FDPs and D-dimers indicate?
Increased fibrinolysis (DIC!)
Severe internal hemorrhage with fibrinolysis
Decreased clearance of FDP by the liver (live dz)
In pathologic conditions, what does a severely increased amount of FDP have on platelets?
Inhibits platelet function (DIC)
What are the patterns of hemorrhage in coagulation disorders?
IM hematomas
Ecchymosis
Bleeding into cavities (thorax/abdomen)
Bleeding into joints
Blood in stool/vomit/urine
A dog is brought into the ER after ingesting a piece of rat bait. He is dyspneic, anemic, weak, and is unable to walk. A blood test confirms that the anemia is regenerative, and PLT counts are normal. You perform a PT, which is prolonged. What is the mechanism of the anemia?
Internal hemorrhage due to warfarin poisining.
*Coumarin is a Vit K antagonist, which affects Vit K dependent coagulation factors X, IX, VII, II.
PT and PTT will both be prolonged
The rat bait dog is decontaminated in clinic and receives a blood transfusion. What is the home treatment plan?
Vitamin K supplements
7 days for Warfarin
3-4 weeks for 2nd generation Warfarin derivatives
(Test PT before discontinuing treatment plan)
What are the potential causes of DIC?
Induction/exposure of tissue factor
Endothelial damage exposing collagen
Proteolytic enzymes
Stagnant blood flow
Snake venoms and trypsin release during pancreatitis cause DIC by what mechanism?
Proteolytic enzymes
Necrosis, sepsis, and neoplasia cause DIC by what mechanism?
Exposure of tissue factor
An ER patient with sepsis is currently suffering from thrombosis and ischemia to the organs, causing renal and respiratory failure. What phase of DIC is this?
1st phase. Hypercoagulation.
The same septic ER patient is now suffering from uncontrolled bleeding, and severely reduced PLTs, coagulation factors, and AT. What phase of DIC is this patient in?
2nd phase. Consumptive phase.
Why is there an increase in FDPs with DIC?
Increased thrombus formation leads to increased fibrinolysis, which leads to increased degradation products.
*FDP concentration this high also inhibits fibrin polymerization, which makes hemorrhage worse in combination with depletion of coagulation factors!
In DIC, mucosal bleeding is due to _____ consumption, while hemorrhage is due to _____ consumption.
platelet; factor
A very sick dog presents to your clinic and your tests indicate that she has a moderate thrombocytopenia, prolonged PT/PTT, increased FDPs and D-dimers, and you see schistocytes on the blood film. What secondary disorder are you worried about and how do you proceed with treatment?
DIC
Try to identify and eliminate the underlying disorder, start fluid therapy, give blood transfusion.
You are about to perform a liver biopsy on a cat with a suspected liver disease. What should you screen for prior to biopsy?
Coagulation disorders
Liver disease = decreased synthesis of coagulation factors or production of dysfunctional factors. These animals may bleed excessively.
A client brings in a foal with a small cut that hasn’t stopped bleeding. PLT counts and PT are normal, but PTT is prolonged. Given the age and history of the patient, you suspect Hemophilia A. Which factor is deficient in this case?
VIII
If a young dog has a deficiency in coagulation factor IX, what inherited disorder does he have?
Hemophilia B
A cat with a prolonged PTT, normal PT, and no signs of bleeding has a deficiency in what coagulation factor?
XII (Hageman’s disease)
