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Flashcards in Hematology and Transfusion Deck (80)

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


Why is Dextran used in microvascular surgery?

- Acts as a volume expander, but in the setting of vascular surgery, it is used because of its interaction with platelets, factor VIII, and endothelial cells to decrease platelet aggregation and blood viscosity.

- these perceived benefits are hypothesized to aid in maintaining graft patency and microcirculation, although its popularity and effectiveness have been questioned.


What are side effects associated with Dextran use?

anaphylaxis, renal failure, coagulopathy, and interference in cross-matching blood.

renal failure from dextran is hypothesized to be from accumulation of dextran molecules in the renal tubules.


What is TRALI?

- acute lung injury within 6 hours of transfusion with features of hypoxemia (with PaO2/FiO2 < 300 mmHg), bilateral pulmonary infiltrates on CXR, and lack of left atrial hypertension

- the MOST COMMON cause of transfusion-related mortality

- can be induced in patients receiving as little as 10-15 mL of plasma.

- more likely in patients receiving platelets compared to FFP and pRBCs

- treatment is supportive (LPV and fluid minimization)


What is the etiology of TRALI, and how do you confirm the diagnosis?

TRALI occurs 2/2 to an immune response of recipient antibodies directed against donor HLA or human neutrophil antigens. Causes an influx of neutrophils into the lungs, with activation of neutrophils and release of inflammatory mediators and development of pulmonary microvascular permeability.

Send a specimen to the blood bank for an antibody-antigen cross match


What is leukoreduction? What are three reasons why leukoreduction is useful?

Refers to removing WBCs from blood products, resulting in a reduction in the number of cytokines produced by leukocytes (cytokines that may incite non-hemolytic febrile transfusion reactions)

- reduces the incidence of nonhemolytic febrile transfusion reactions.

- reduces bacterial transmission

- reduces HLA alloimmunization


What is Dextran?

- a branched-chain polysaccharide used as an antithrombotic, to reduce blood viscosity, and as a volume expander in anemia.


Why use CellSaver blood?

- CellSaver blood allows for blood that is lost on the surgical field to be collected and processed by washing and centrifugation to obtain RBCs for autotransfusion.

- commonly used in procedures where large amounts of blood are expected to be lost.


What is the advantage to using CellSaver blood?

- avoids complications of transfusing allogeneic blood, mainly transfusion reactions, such as hemolytic reactions, and transmission of bloodborne pathogens


What is the risk of massive transfusion with CellSaver blood?

During the processing, blood components such as platelets and coagulation factors are lost --> massive transfusion with CellSaver blood will result in a dilutional coagulopathy


What is the definition of massive transfusion?

- Giving more than 10 units of blood or the patient's total blood volume over a period of 24 hours


What are complications of massive transfusion?

Dilutional coagulopathy, DIC, citrate toxicity, hypothermia, acidosis


What is citrate toxicity?

- Typically occurs in the setting of massive transfusion. Occurs when blood is given more quickly than the liver can metabolize the citrate.

Citrate is one of the components of CPDA. Citrate acts as an anticoagulant by chelating calcium in stored blood. Massive transfusion of red cells introduces large amounts of citrate into the circulation, which can bind free calcium and cause HYPOCALCEMIA.

Hypocalcemia induced by citrate toxicity generally corrects itself because the liver can rapidly metabolize citrate at the rate of 3 gm (contained in 1 pack of pRBCs) every 5 minutes. In cases where there is liver dysfunction or low perfusion states, liver dysfunction is impaired.


What are signs of citrate toxicity?

Hypotension, narrow pulse pressure, elevated CVP, elevated end-diastolic pressure


If a patient has normal liver function, how long will it take the patient to metabolize citrate after receiving 10 units of pRBCs?

- Each unit of pRBC contains 3 gm of citrate.
- It takes 5 minutes to metabolize 3 gm of citrate
- Will take the patient 55 minutes to metabolize all of the citrate after receiving 10 units of pRBCs


What is PCC?

- Prothrombin complex concentrate

- composed of vitamin K dependent factors II, VII, IX, and X derived from pooled plasma.


What are advantages to using PCC as opposed to FFP?

- decreased risk of viral trasmission because it is filtered, heat-inactivated, and/or treated with solvent detergent
- does not have to be ABO-type specific because antibodies and red blood cells are removed during the purification process
- useful in reversing warfarin anticoagulation because it provides replacement facotrs for factors II, IX, and X deficiencies.


What is the main risk with PCC administration?

Thrombus formation.


What is added to PCC to prevent the main risk associated with its administration?

Thrombosis is the main risk, proteins C and S, antithrombin, and heparin are added to most formulations to reduce thrombogenicity.


In terms of timing and volume, how is PCC advantageous compared to FFP?

A dose of PCC can be reconstituted in as little as 20 cc's and its effects are seen within 10 minutes.

Conversely, FFP must be thawed and usually requires an infusion of at least 2-4 units (~200 cc/bag) before reduction of INR is achieved.


In which class of patients is PCC contraindicated?

Patients with heparin-induced thrombocytopenia and DIC.


How quickly are the effects of PCC seen? How much volume of PCC is needed?

As little as 20 cc's can be given, effects seen in as little as 10 minutes


How much volume is administered with 4 bags of FFP?

approximately 800 cc's (1 unit of FFP contains approximately 200-250 ccs)


What is the INR of FFP?

Approximately 1.6


Does FFP need to be ABO compatible?



Go to this website for good info on FFP:



What is cyroprecipitate?

Derived as a white insoluble precipitate from FFP as it is thawing.


What is in cryoprecipitate?

Contains large amounts of factor VIII, fibrinogen, vWF, and fibronectin


T or F: Cryoprecipitate is the only adequate fibrinogen concentrate available for intravenous use.



In what states is cryoprecipitate useful?

fibrinogen deficiency states like DIC, liver failure, and massive transfusion and factor VIII (hemophilia A deficiency)


Does cryoprecipitate need to be ABO-type crossmatched?



Good website with info on cryoprecipitate:



How does albumin work?

The oncotic pressure of albumin 25% solution is about four times higher than that of normal human serum, so it will expand the plasma volume if interstitial water is available for an inflow through the capillary walls.


T or F: once the total volume of red cell transfusion exceeds 1 patient blood volume, or approximately 10-12 units, non-group O patients should continue to be transfused with type O blood.

True- type O blood contains anti-A and anti-B antibodies, which, after massive transfusion, may be present in quantities sufficient to reach with transfused non-O units.

Type specific units may be transfused if anti-A and anti-B antibody titers are sufficiently low.


What are the four pertinent parameters in a thromboelastograph?

1- R-value- the time until the first evidence of a clot is detected
2- Maximum amplitude- a reflection of clot strength
3- Alpha angle- the tangent of the curve made as the K is reached and offers similar information to K
4- K-value- the time from the end of R until the clot reaches 20mm --> represents the speed of clot formation



T or F: in CPR, a severe metabolic and respiratory acidosis results 2/2 to generation of significant amounts of lactic acid and decreased CO2 transport from the tissues to the lungs.



T or F: the poor or absent perfusion and oxygen delivery of cardiac arrest quickly causes a shift in physiologic mechanisms from aerobic to anaerobic glycolysis.

True- This leads to profound metabolic acidosis due to both the generation of significant amounts of lactic acid and decreased carbon dioxide transport from the tissues to the lungs.


T or F: thromboelastography reflects the true coagulability of blood and not specific factors by measuring viscoelastic properties of blood as clot formation progresses.



What is DIC?

Disseminated intravascular coagulation (DIC) is a pathological process characterized by the widespread activation of the clotting cascade that results in the formation of blood clots in the small blood vessels throughout the body. This leads to compromise of tissue blood flow and can ultimately lead to multiple organ damage. In addition, as the coagulation process consumes clotting factors and platelets, normal clotting is disrupted and severe bleeding can occur from various sites.

In the setting of sepsis, immune complexes, endotoxin, and cytokines cause activation of various parts of the clotting cascade, leading to widespread fibrin formation and thrombosis. Eventually as factors and platelets are consumed in the formation of thromboses, there is a factor deficiency and thrombocytopenia, leading to coagulopathy. The process of widespread thrombosis also leads to increased fibrin breakdown by plasmin, leading to increased D-dimers.

Treatment is treating the cause, also platelets, FFP, cryoprecipitate.


T or F: the PaCO2 of blood decreases as it cools, resulting in an increase in the pH of the blood.



Type 1 vWF: less vWF --> DDAVP increases levels
Type 2 vWF: weird vWF --> DDAVP produces more weird vWF, leading to thrombosis and thrombocytopenia
Type 3 vWF: extremely low vWF --> DDAVP doesn't increase it enough to make a difference, must give cryoprecipitate



T or F: febrile reactions occur due to recipient antibodies to donor WBCs.

Short lived, can be treated with antipyretics, and not a reason to stop


List some clinical characteristics of TRALI.

- occurs w/i 2 hours
- resolves within 48 hours
- clinically similar to ARDS --> capilary leak syndrome causing significant non-cardiogenic pulmonary edema


HIV: 1:2,000,000
HepB: 1:200,000
HepC: 1:2,000,000



What is the most common cause of transfusion-related mortality?

TRALI, which causes more deaths than acute hemolytic reactions from ABO blood type error.


T or F: acute hemolytic reactions are most frequently due to clerical error.



T or F: infectious complications such as sepsis occur usually from bacterial infection most common after transfusion of platelets due to storage at room temperature to maintain platelet function.

True- gram negative bacteria are frequent causes of transfusion-associated sepsis as well. Gram positive organisms are more likely platelet contaminants.


T or F: in patients with known IgA deficiecy, what is a necessary step of blood products prior to transfusion?

All blood products must be washed in normal saline to remove as much contaminating IgA as possible. IgA deficient patients typically have Anti-IgA antibodies that react to blood products containing small amounts of IgA.

Hence, pts should only receive cells that have been washed to remove as much of the contaminating IgA as possible.


Desmopressin administration increases the activity of which factors?

Factor VIII, XII, and vWF.