Flashcards in Blood Products and Coagulation Deck (47):
What components of blood are available?
Whole blood, pRBC, platelets, FFP, cryoprecipitate, WBCs
What is CPDA?
Used in pRBC storage.
Citrate as anticoagulant
Phosphate as buffer
Dextrose as RBC energy source
Adenosine as precursor for ATP synthesis
How much does one unit of pRBCs raise hemoglobin and Hct levels?
Hemoglobin: 1 mg/dl
What is the purpose of an RBC transfusion?
To maximize oxygen delivery to critically ill tissues
What is a hemolytic transfusion reaction?
Occurs when ABO or Rh mismatched blood is given. May occur with as little as 10 cc's of administered blood. Causes DIC.
List classic findings in a hemolytic transfusion reaction.
Fever, chills, back or flank pain, chest pain, dyspnea, hypotension, oliguria, hemoglobinuria. Intraoperatively, may be heralded by sudden bleeding in a previously dry field.
What is FFP?
FFP contains fibrinogen; prothrombin; factors V, VII, VIII, IX, and XIII; antithrombin III; and proteins C and S.
List at least 5 indications to give FFP.
1- Coagulopathy 2/2 a congenital deficiency, especially of factor II, V, VII, VIII, X, XI, or XIII
2- Coagulopathy 2/2 acquired deficiency of multiple factors, such as severe liver disease, DIC, or vitamin K depletion
3- Dilutional coagulopathy in a massively transfused patient (more than one blood volume)
4- Reversal of warfarin
5- Treatment of antithrombin III deficiency
What is cryoprecipitate?
- Prepared from FFP by slow thawing at 4–6 degrees celcius and centrifuging it.
- Contains high concentrations of factor 8 and 13, von Willebrand factor, and fibrinogen.
List at least 4 indications for giving cryoprecipitate.
1- Hypofibrinogenemia (fibrinogen level less than 100 mg/dL)
2- Von Willebrand’s disease
3- Hemophilia A (factor VIII deficiency)
4- Bleeding due to thrombolytic therapy
Cryoprecipitate can be used to promote hemostasis in a bleeding patient; in most
circumstances, however, it is preferable to give FFP, which contains more of the essential clotting factors.
What is measured by prothrombin time?
PT assesses the activity of factor VII, which is involved in the extrinsic coagulation pathway only. It is prolonged in patients with liver disease and patients who are deficient in vitamin K.
What is measured by partial thromboplastin time (PTT)?
- Assesses activities of the intrinsic coagulation pathway, which includes factors VIII. IX, XI, and XII.
- A prolonged PTT with a normal PT suggests an inherited defect in coagulation.
What is the most common inherited factor deficiency?
Hemophilia A, a deficiency of factor VIII (about 75%), followed by hemophilia B, a deficiency of factor IX (about 20%).
How does warfarin work?
Warfarin inhibits the conversion of vitamin K to its active form. This inhibition interferes with the hepatic synthesis of vitamin K–dependent clotting factors II, VII, IX, and X. Warfarin primarily prolongs PT.
How does heparin work?
Heparin binds to and activates antithrombin III, which in turn inhibits several coagulation
enzymes, including thrombin and activated factors X, XII, XI, and IX. The biological half-life of
heparin is 30–60 minutes; its effects can be reversed within 2–4 hours after an infusion is
stopped. Heparin prolongs PTT.
What is low-molecular-weight heparin (LMWH)?
LMWH is a fragment produced by the chemical breakdown of heparin and is 1/3rd the size of heparin. It exerts its anticoagulant effect by binding with antithrombin III and inhibiting several coagulation enzymes. LMWH principally inhibits activated factor X. LMWHs have more predictable dose response, better bioavailability, and a longer plasma half-life than regular heparin.
What are three major differences between standard heparin and LMWH?
1- LMWH has a longer half-life and thus can be administered once daily.
2- LMWH gives a more predictable anticoagulant response at high doses and thus can be administered without monitoring (i.e., serial activated PTTs).
3- LMWH produces fewer bleeding complications than standard heparin at equivalent antithrombotic doses.
What processes form the normal hemostatic process?
Primary hemostasis, secondary hemostasis, fibrinolysis
What is primary hemostasis?
- Involves the formation of the platelet plug.
Within seconds of vascular injury, platelets become activated and adhere to the subendothelial collagen layer of the denuded vessel via glycoprotein receptors; this interaction is stabilized by von Willebrand’s factor (vWF).
Collagen and epinephrine activate phospholipases A and C in the platelet plasma membrane, resulting in formation of thromboxane A2 (TXA2) and degranulation, respectively. TXA2 is a potent vasoconstrictor that promotes platelet aggregation.
Platelet granules contain adenosine diphosphate (ADP), TXA2, vWF, factor V, fibrinogen, and fibronectin. ADP alters the membrane glycoprotein IIb/IIIa, facilitating the binding of fibrinogen to activated platelets. Thus a platelet plug is constructed and reinforced.
What is secondary hemostasis?
- Involves the formation of a fibrin clot.
The fibrin network binds and strengthens the platelet plug. Fibrin can be formed via two pathways (intrinsic and extrinsic) and involves activation of circulating coagulation precursors. Regardless of which pathway is triggered, the coagulation cascade results in the conversion of fibrinogen to fibrin.
What are the intrinsic and extrinsic coagulation pathways?
Traditionally these two pathways have been viewed as separate mechanisms that merge after the formation of activated factor X. This rigid division has lost absolute validity because of the crossover of many factors.
What is fibrinolysis?
The fibrinolytic system is activated simultaneously with the coagulation cascade and functions to maintain the fluidity of blood during coagulation. It also serves in clot lysis once tissue repair begins. When a clot is formed, plasminogen is incorporated and then converted to plasmin by tissue plasminogen activator (tPA) and fragments of factor XII. Endothelial cells release tPA in response to thrombin. Plasmin degrades fibrin and fibrinogen into small fragments. These fibrin degradation products possess anticoagulant properties because they compete with fibrinogen for thrombin; they are normally cleared by the monocyte-macrophage system.
Why doesn't blood coagulate in normal tissues?
Coagulation is limited to injured tissue by localization of platelets to the site of injury and maintenance of normal blood flow in noninjured areas. The monocyte-macrophage system scavenges activated coagulation factors in regions of normal blood flow. Normal vascular endothelium produces prostacyclin (prostaglandin I2), which is a potent vasodilator that inhibits platelet activation and helps confine primary hemostasis to the injured area.
What is an acceptable preoperative platelet count?
- Normal platelet count = 150,000- 400,000/mm3.
- Thrombocytopenia = count of <20,000/mm3.
- The minimal recommended platelet count before surgery is 75,000/mm3.
What are normal bleeding times? What is an abnormal bleeding time?
Normal bleeding times range from 4 to 9 minutes, and a bleeding time >1.5 times normal (>15 minutes) is considered significantly abnormal.
List causes of thrombocytopenia.
- Iatrogenic- massive blood transfusion, HIT
- Decreased platelet production- cancer, chemo
- Increased platelet destruction- hypersplenism, DIC
List functional platelet abnormalities.
Inherited- von Willebrand's disease
Acquired- uremia, cirrhosis, aspirin and NSAIDs
How does aspirin act as an anticoagulant?
Primary hemostasis is controlled by the balance between the opposing actions of two prostaglandins, TXA2 and prostacyclin. Depending on the dose, aspirin produces a differential effect on prostaglandin synthesis in platelets and vascular endothelial cells. Lower doses preferentially inhibit platelet COX, impeding production of TXA2 and inhibiting platelet aggregation. The effect begins within 2 hours of ingestion.
Because platelets lack a cell nucleus and cannot produce protein, the effect LASTS FOR THE ENTIRE LIFE of the platelet (7 to 10 days). NSAIDs have a similar but more transient effect than aspirin, lasting for only 1 to 3 days after cessation of use.
How much does one unit of FFP decrease prothrombin time by?
1 unit of FFP decrease the prothrombin time by 2 seconds
How does Vitamin K deficiency affect coagulation?
Factors II, VII, IX, X are synthesized in the liver and undergo vitamin-K dependent carboxylation to their active forms. --> WITHOUT VITAMIN K, the factors are produced but are NOT functional.
Which factor is first affected by Vitamin K deficiency (aka, which factor has the shortest half-life)?
Factor VII of the extrinsic pathway, because factor VII has the shortest half-life.
How long does it take for the administration of subq vitamin K to reverse Vitamin K deficiency?
How does heparin act as an anticoagulant?
Heparin accelerates the interaction between antithrombin III and factors II, X, XI, XII, and XIII, effectively more quickly neutralizing each.
What is the half-life of heparin in a normothermic patient?
What class of patients are resistant to the effects of heparin?
Patients with low levels of antithrombin III.
What is in prothrombin complex concentrates?
- Vitamin K dependent factors II, VII, IX, X
What is prothrombin complex concentrate derived from?
Does PCC carry the risk of viral transmission?
Yes, but not as great as with traditional blood products because it is filtered, heat-inactivated, and/or treated with solvent detergent
Does PCC have to be ABO type specific?
No, because antibodies and red blood cells are removed during the purification process
Is PCC useful for treating hemophilia A? Hemophilia B?
No for hemophilia A (which is factor VIII deficiency)
Yes for hemophilia B (which is factor IX deficiency)- PCC has factor IX
What is the main risk associated with administering PCC?
Risk of thrombosis, but it is RARE. Proteins C and S, anti-thrombin, and heparin are added to most formulations to reduce thrombogenicity
In what group of patients is PCC contraindicated?
Patients with heparin-induced thrombocytopenia and DIC
True or false: a dose of PCC can be reconstituted in as little as 20 cc's for urgent reversal of warfarin anticoagulation. The effects may be seen within 10 minutes
True. Conversely, FFP must be thawed and requres an infusion of at least 2-4 units (~200 cc/bag) before reduction of INR is achieved.
True or false: reversal of anticoagulation with PCC is more complete than reversal with FFP
True. There is a higher frequency of normalization of INR < 1.5 compared to FFP.
True or false: both FFP and PCC provide short term reversal of anticoagulation because the replacement factors have half-lives in the range of hours.
True- to maintain long term reversal of anticoagulation, vitamin K administration is recommended with both FFP and PCC.
Which blood product is most likely to induce citrate toxicity?
5- whole blood
FFP has the highest concentration of citrate because more citrate is needed to prevent coagulation of clotting factors. This is important because rapid administration of FFP can lead to hypotension and prevent normal clotting.