Hematology and Transfusion Flashcards
Why are patients at risk of thrombus when they are initially started on warfarin?
When warfarin is newly started, it may promote clot formation temporarily because of an acquired reduction in protein C and S levels, which are also dependent on vitamin K activity. Protein C and S deficiencies increase the risk of venous thromboembolism.
Warfarin causes decline in protein C levels in first 36 hours. In addition, reduced protein S levels lead to a reduction in activity of protein C (for which it is the co-factor) and therefore reduced degradation of factor Va and factor VIIIa. Although loading doses of warfarin over 5 mg also produce a precipitous decline in factor VII, resulting in an initial prolongation of the INR, full antithrombotic effect does not take place until significant reduction in factor II occurs days later. The hemostasis system becomes temporarily biased towards thrombus formation, leading to a prothrombotic state.
Thus, when warfarin is loaded rapidly at greater than 5 mg per day, it is beneficial to co-administer heparin, an anticoagulant that acts upon antithrombin and helps reduce the risk of thrombosis, with warfarin therapy for four to five days, in order to have the benefit of anticoagulation from heparin until the full effect of warfarin has been achieved.
What is bridging anticoagulation?
Refers to giving a short-acting blood thinner, usually LMWH SQ for 10-12 days around the time of the surgery/procedure, when warfarin is interrupted and its anticoagulant effect is outside a therapeutic range.
Aims to reduce risk for developing blood clots, such as stroke, but may also increase risk for developing potentially serious bleeding complications after surgery.
How is bridging anticoagulation given?
After warfarin is stopped, 5 to 6 days before surgery (to allow sufficient time for its anticoagulant effect to wane), bridging anticoagulation is started 3 days before surgery, with the last dose given 24 hours before surgery. After surgery, bridging is resumed no earlier than 24 hours after surgery; at the same time, warfarin is restarted. Bridging is continued, typically for 4 to 6 days, until the anticoagulant effect of warfarin has resumed and the blood is sufficiently thinned again.
What is von Willebrand’s disease?
- The most common hereditary coagulation abnormality described in humans.
- Arises from a qualitative or quantitative deficiency of von Willebrand factor (vWF), which is required for platelet adhesion.
- The various types of vWD present with varying degrees of bleeding tendency, usually in the form of easy bruising, nosebleeds and bleeding gums. Women may experience heavy menstrual periods and blood loss during childbirth.
What does prothrombin time (PT) measure?
- Measures the EXTRINSIC and final common pathways of the coagulation cascade
- normally 11-14 seconds
- measures the activity of fibrinogen, prothrombin, and factors V, VII, and X
- relatively short half-life of factor VII (4-6 hours) makes PT useful in evaluating hepatic synthetic function of patients with acute or chronic liver disease
- warfarin measurement is likely the most common indication for measurement
What does partial thromboplastin time (PTT) evaluate?
- the INTRINSIC and common coagulation pathways and adequacy of all coagulation factors except XIII and VII.
- Usually abnormal if any factor level drops below 25-40% of normal
- commonly used to monitor heparin therapy
- increased in deficiency of any individual coagulation factor except XIII and VIII
If you have a patient with von willebrand’s disease, what information should you seek?
You should ask about which type of vWD this patient has, as management changes depending on the type of vWD. Treatment will vary from giving DDAVP to Factor VIII
- Type 1: mildest and most common form, ask about bleeding after tooth extraction, gingival oozing, hemarthrosis
- Type 2- defective vWF
- Type 3- absent vWF and low factor VIII levels
If you have a patient with known type III vWD, what should you give preoperatively? What if there is none of that product?
- Factor VIII concentrate
- Cryoprecipitate is derived from FFP but has HIGHER concentrations of fibrinogen, vWF and factor VIII.
What is hemophilia A?
- a sex-linked inherited bleeding disorder in which factor VIII levels are markedly reduced or non-existent
- Factor VIII is part of the intrinsic blood clotting pathway, which can prolong the PTT dpeneding on the severity of the hemophilia.
How do you treat hemophilia A preoperatively?
- Replace factor VIII levels to 80-100% with continued replacement up to 2 weeks s/p surgery.
- The patient may have inhibitors towards Factor VIII –> check for inhibitors with the Bethesda inhibitor assay
- DDAVP may be given to stimulate production of factor VIII to more than 3x the current level
What is hemophilia B?
- Deficiency of factor IX
- sex-linked inheritance
- DDAVP has no effect on Factor IX levels
Hemophilia A factor deficiency?
Factor VIII
Hemophilia B factor deficiency?
Factor IX
Hemophilia A and B inheritance?
recessive sex-linked
Hemophilia A and B blood test results
- prolonged PTT, normal bleeding time and PT
Hemophilia A treatment?
Purified Factor VIII concentrates, cryoprecipitate, and DDAVP
Patients need 50% Factor VIII activity for minor surgery and 100% activity for major surgery.
Factor VIII concentrate delivers 40 units/cc, cryo delivers 20 units/cc, FFP has 1 unit/cc. DDAVP upregulates natural production of factor VIII
Hemohilia B treatment?
Purified Factor IX concentrates, FFP, PCC
What is in cryoprecipitate?
Factor VIII, fibrinogen, and vWF.
Has NO factor IX, so ineffective in treatment of hemophilia B.
How does clopidogrel work?
- irreversibly inhibits the P2Y receptor –> prevents cross-linking of platelets to fibrin, which is the first step in the clotting cascade pathway.
A part of dual platelet therapy along with aspirin. Decreases cross-linking of platelets to fibrin.
How does aspirin work?
- irreversibly inactivates the COX enzyme –> blocks the formation of thromboxane A1 in platelets, further decreasing platelet aggregation.
A part of dual platelet therapy along with clopidogrel. Decreases platelet aggregation.
Why is desmopressin (DDAVP) an effective treatment for von Willebrand’s disease?
- DDAVP stimulates the release of stored vWF and Factor VIII from the vascular endothelium within 30-60 min for a continued effect of up to 24 hours.
- Indicated for central DI, control of bleeding in mild hemophilia A, and certain subtypes of vWD.
- Used in uremic patients to reduce bleeding.
Why can patients become coagulopathic in the setting of spine surgery?
Blood loss and pooling at the surgical site puts patients at risk for consumptive coagulopathy.
If clinical suspicion of microvascular bleeding exists, transfusion of FFP is indicated to maintain hemostasis.
What is hetastarch?
- a synthetic colloid in the family of hydroxyethyl starches.
How does hetastarch work?
- creates an osmotic gradient within the intravascular space that achieves effective volume expansion using less volume than crystalloid.
How long does hetastarch work?
Its volume expansion properties last 24 hours before excretion by the kidneys.
What are side effects associated with hetastarch?
Hetastarch has a high degree of hydroxyethylation to slow the rate of metabolism and elimination. However, it is this property that is responsible for its numerous side effects, including:
- coagulopathy
- anaphylactic reactions
- renal impairment
- accumulation of byproducts
Why does hetastarch produce a von Willebrand disease like syndrome?
at high doses (> 20 mL/kg), hetastarch interacts with platelets and decreases factor VIII and von willebrand factor.
How can hetastarch cause pruritis?
- Repeated administration leads to development of byproducts that accumulate in RES and peripheral nerves
- Hetastarch-induced pruritus is an intense itching, lasting for as long as one year, occurring following hetastarch IV infusion for vascular insufficiency.
- There is no treatment for the itch.
Why are the subsequent generation of hetastarches (ie the pentastarches, tetrastarches) demonstrate similar volume expansion profiles with much improved safety profiles?
- little to no effect on hemostasis, renal impairment, or accumulation of byproducts
- new generation has less development of byproducts
- have a lower molecular weight and a lower molar substitution ratio than older hetastarches
Does hetastarch affect PTT?
One liter of 6% solution (Hespan) reduces factor VIII level by 50% and will prolong aPTT.
What is a bleeding time?
- a test to assess platelet function
- done by making a forearm cut and observing the duration of bleeding until hemostasis occurs
- typically ranges from 2-9 minutes
What are the most common causes of prolonged bleeding?
- aspirin, NSAIDs, DIC, hypofibrinogenemia, thrombocytopenia
