Blood Products and Coagulation

Question 1

What components of blood are available?

Answer 1

Whole blood, pRBC, platelets, FFP, cryoprecipitate, WBCs

Question 2

What is CPDA?

Answer 2

Used in pRBC storage.

Citrate as anticoagulant
Phosphate as buffer
Dextrose as RBC energy source
Adenosine as precursor for ATP synthesis

Question 3

How much does one unit of pRBCs raise hemoglobin and Hct levels?

Answer 3

Hemoglobin: 1 mg/dl
Hct: 3%

Question 4

What is the purpose of an RBC transfusion?

Answer 4

To maximize oxygen delivery to critically ill tissues

Question 5

What is a hemolytic transfusion reaction?

Answer 5

Occurs when ABO or Rh mismatched blood is given. May occur with as little as 10 cc’s of administered blood. Causes DIC.

Question 6

List classic findings in a hemolytic transfusion reaction.

Answer 6

Fever, chills, back or flank pain, chest pain, dyspnea, hypotension, oliguria, hemoglobinuria. Intraoperatively, may be heralded by sudden bleeding in a previously dry field.

Question 7

What is FFP?

Answer 7

FFP contains fibrinogen; prothrombin; factors V, VII, VIII, IX, and XIII; antithrombin III; and proteins C and S.

Question 8

List at least 5 indications to give FFP.

Answer 8

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

Question 9

What is cryoprecipitate?

Answer 9

• 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.

Question 10

List at least 4 indications for giving cryoprecipitate.

Answer 10

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.

Question 11

What is measured by prothrombin time?

Answer 11

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.

Question 12

What is measured by partial thromboplastin time (PTT)?

Answer 12

• 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.

Question 13

What is the most common inherited factor deficiency?

Answer 13

Hemophilia A, a deficiency of factor VIII (about 75%), followed by hemophilia B, a deficiency of factor IX (about 20%).

Question 14

How does warfarin work?

Answer 14

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.

Question 15

How does heparin work?

Answer 15

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.

Question 16

What is low-molecular-weight heparin (LMWH)?

Answer 16

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.

Question 17

What are three major differences between standard heparin and LMWH?

Answer 17

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.

Question 18

What processes form the normal hemostatic process?

Answer 18

Primary hemostasis, secondary hemostasis, fibrinolysis

Question 19

What is primary hemostasis?

Answer 19

• 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.

Question 20

What is secondary hemostasis?

Answer 20

• 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.

Question 21

What are the intrinsic and extrinsic coagulation pathways?

Answer 21

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.

Question 22

What is fibrinolysis?

Answer 22

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.

Question 23

Why doesn’t blood coagulate in normal tissues?

Answer 23

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.

Question 24

What is an acceptable preoperative platelet count?

Answer 24

• 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.

Question 25

What are normal bleeding times? What is an abnormal bleeding time?

Answer 25

Normal bleeding times range from 4 to 9 minutes, and a bleeding time >1.5 times normal (>15 minutes) is considered significantly abnormal.

Question 26

List causes of thrombocytopenia.

Answer 26

• Iatrogenic- massive blood transfusion, HIT
• Decreased platelet production- cancer, chemo
• Increased platelet destruction- hypersplenism, DIC

Question 27

List functional platelet abnormalities.

Answer 27

Inherited- von Willebrand’s disease

Acquired- uremia, cirrhosis, aspirin and NSAIDs

Question 28

How does aspirin act as an anticoagulant?

Answer 28

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.

Question 29

How much does one unit of FFP decrease prothrombin time by?

Answer 29

1 unit of FFP decrease the prothrombin time by 2 seconds

Question 30

How does Vitamin K deficiency affect coagulation?

Answer 30

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.

Question 31

Which factor is first affected by Vitamin K deficiency (aka, which factor has the shortest half-life)?

Answer 31

Factor VII of the extrinsic pathway, because factor VII has the shortest half-life.

Question 32

How long does it take for the administration of subq vitamin K to reverse Vitamin K deficiency?

Answer 32

6-24 hours

Question 33

How does heparin act as an anticoagulant?

Answer 33

Heparin accelerates the interaction between antithrombin III and factors II, X, XI, XII, and XIII, effectively more quickly neutralizing each.

Question 34

What is the half-life of heparin in a normothermic patient?

Answer 34

90 minutes

Question 35

What class of patients are resistant to the effects of heparin?

Answer 35

Patients with low levels of antithrombin III.

Question 36

What is in prothrombin complex concentrates?

Answer 36

• Vitamin K dependent factors II, VII, IX, X

Question 37

What is prothrombin complex concentrate derived from?

Answer 37

pooled plasma

Question 38

Does PCC carry the risk of viral transmission?

Answer 38

Yes, but not as great as with traditional blood products because it is filtered, heat-inactivated, and/or treated with solvent detergent

Question 39

Does PCC have to be ABO type specific?

Answer 39

No, because antibodies and red blood cells are removed during the purification process

Question 40

Is PCC useful for treating hemophilia A? Hemophilia B?

Answer 40

No for hemophilia A (which is factor VIII deficiency)

Yes for hemophilia B (which is factor IX deficiency)- PCC has factor IX

Question 41

What is the main risk associated with administering PCC?

Answer 41

Risk of thrombosis, but it is RARE. Proteins C and S, anti-thrombin, and heparin are added to most formulations to reduce thrombogenicity

Question 42

In what group of patients is PCC contraindicated?

Answer 42

Patients with heparin-induced thrombocytopenia and DIC

Question 43

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

Answer 43

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.

Question 44

True or false: reversal of anticoagulation with PCC is more complete than reversal with FFP

Answer 44

True. There is a higher frequency of normalization of INR < 1.5 compared to FFP.

Question 45

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.

Answer 45

True- to maintain long term reversal of anticoagulation, vitamin K administration is recommended with both FFP and PCC.

Question 46

Which blood product is most likely to induce citrate toxicity?

1- cryoprecipitate
2- pRBC
3- FFP
4- platelets
5- whole blood

Answer 46

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.

Question 47

How do rats die when they are exposed to rodenticide?

Answer 47

• Rodenticides contain long acting anticoagulants called superwarfarins. Bioavailability is close to 100%.
• Superwarfarins cause lethal bleeding within several days because have structural similarities to vitamin K and competitively inhibit the enzymatic reduction of vitamin K to its active form –> decrease plasma levels of vitamin K dependent clotting factors II, VII, IX, and X.
• The anticoagulant effect takes some time to develop, as the circulating factors themselves are not affected. Half lives of VII, IX, X and II respectively are 6, 24, 40 and 60 hours. Severe bleeding symptoms occur a few days after rodenticide ingestion.