Physiology-Treatment of Coagulation Disorders Flashcards
Platelet type bleeding
From mucous membranes (nose bleeds, blood in urine, external cuts)
Factor type bleeding
Deeper joint bleeds and muscle bleeds
What type of bleeding do people with vWF deficiency presents with?
Platelet-type. This is because vWF is necessary for platelet aggregation and adherence to endothelium.
Why is PTT extended if a patient has vWF deficiency?
vWF complexes with factor VIII. When vWF is deficient, so is factor VIII which is in the intrinsic pathway.
What happens in primary hemostasis?
Vessel injury -> platelet adhesion -> platelet activation -> platelet aggregation -> platelet plug
What happens in secondary hemostasis?
Activation of coagulation cascade and formation of fibrin clot.
Deficiency in what factors of the coagulation cascade will not cause a bleeding deficiency?
Kallikrein, prekallikrein and factor XII. Note that factor XII will have an elevated PTT, but does not present with a bleeding disorder.
A patient presents with spontaneous deep tissue bleeds. He has several brothers, uncles and cousins with the same condition. What are the most common bleeding disorders?
Hemophilia A (VIII) and B (IX). Both are X-linked recessive.
What is a specific test for DIC?
D-dimer (indicates that fibrinogen has been activated by thrombin because you can’t get split products until after the fibrin network has formed)
A patient presents with a stump umbilical cord and poorly healing wounds. PT and PTT are normal. What clotting factor could be deficient?
Factor XIII. It is responsible for crosslinking of fibrin molecules to form the clot.
What are the acquired factor deficiencies?
Vit K (II, VII, IX, X, C & S are present, but not activated), liver failure (not producing factors, except VIII) and DIC (all factors are being used up)
How do you treat someone who is bleeding and can’t stop bleeding due to vitamin K deficiency?
Give subQ vitamin K and fresh frozen plasma because it takes time for vitamin K to actually activate the clotting factors.
A patient is brought into the ED after a motorcycle accident. He is bleeding and has a history of bleeding easily, but is unconscious. How do you treat him? What risks does this treatment carry?
Fresh frozen plasma is used when the bleeding disorder diagnosis is unknown, multiple factors are needed or the concentrated factor product is not available. He is at risk for volume overload, infection and allergic reactions.
What are the main infectious complications associated with transfusions?
Bacteria, viral (hepatitis, HIV, parvovirus) and prion diseases (CJD)
What happens when FFP is thawed out at 4 degrees C in the refrigerator? Why is this useful?
You get cryoprecipitate: plasma fraction concentrated for fibrinogen, VIII, XIII and vWF. Although it still carries risk for allergic reactions and infection, it is less volume than FFP and risk for volume overload is decreased.
Why does PT become prolonged 1st in liver disease?
Factor VII has the shortest half life. Factor XIII has the longest.
How do you need to dose factor replacement therapy?
Frequency (because different factors have different half lives) and amount (because some don’t require as much to become hemostatic)
What determines the severity of hemophilia A and B?
5% = mild. And then carriers are mostly asymptomatic.
What type of plasma do you use to treat hemophilia A?
Monoclate P. Plasma derived factor concentrate (filtered by affinity chromatography for factors) from a large pool of screened donors. The concentrate is the virally inactivated.
How do you treat hemophilia A and B?
Give recombinant factor VIII or IX. 1 unit/kg raises activity level 2% with a half life of 8-12 hours. It is given by slow IV infusion. For mild bleeds (non-life threatening hematoma), you raise activity to 40%. For severe bleeds (deep muscle or retroperitoneal), you raise activity to 100%.
A patient with hemophilia A comes in bleeding. You want to get his factor VIII level up to 30%. How many units should you give if he weighs 50 kg?
Dose of FVIII = Wt x Desired % increase x 0.5. 50 x 30 x 0.5 = 750. But you’d actually give the entire vile so you don’t waste factor.
Why might recombinate be preferable to monoclate P in treatment of hemophilia A?
Recombinate is a genetically engineered recombinate factor VIII and decreases risk for infection or prion disease. Monoclate P is a plasma derived factor concentrate.
Why might advate be preferable to recombinate in treatment of hemophilia A?
Advate is the second generation recombinate lacking the B domain, which means that you don’t need albumin to stabilize it at all. The makes the risk for infection or prion disease 0.
What is the new drug that helps prolong the action of replacement factor VIII?
It is complexed with IgG, which lasts longer in the blood stream.
