LE 2 - Hemostasis

Question 1

1. Which of the following is NOT one of the four major physiological events of hemostasis?
   A. Vasodilation
   B. Platelet aggregation
   C. Clot Formation
   D. Fibrinolysis

Answer 1

A. Vasodilation

Hemostasis Process:
- Purpose: Limits blood loss from an injured vessel.
- Four Physiologic Events:
1. Vasoconstriction
2. Platelet aggregation
3. Clot formation
4. Fibrinolysis
- Two Cascades: Extrinsic and Intrinsic.
- Both lead to the conversion of prothrombin to thrombin to fibrin, crucial for clot formation.

The process of hemostasis is a coordinated response to injury that aims to prevent excessive blood loss. Schwartz’s Principles of Surgery outlines these primary events:
- Vasoconstriction: An immediate response after vascular injury, reducing blood flow and minimizing loss.
- Platelet Aggregation: Platelets adhere to the injured site and then aggregate to form a “platelet plug” at the wound.
- Clot Formation: Activation of the coagulation cascades (both intrinsic and extrinsic pathways) leads to the formation of fibrin, which strengthens the platelet plug into a solid clot.
- Fibrinolysis: Once the vessel heals, the body needs to remove the clot. Fibrinolysis is the process where the clot gets dissolved.

Vasodilation is not a primary event of hemostasis. Instead, it refers to the widening of blood vessels, which would be counterintuitive in a hemostatic response as it would increase blood flow.

Question 2

2. Which of the following is required for platelet adherence to injured endothelium?
   A. Thromboxane A2
   B. Glycoprotein (GP) IIb/IIIa
   C. Adenosine diphosphate (ADP)
   D. Von Willebrand factor (vWF)

Answer 2

D. Von Willebrand factor (vWF)

2. Platelet Adherence
Platelet adherence to the injured vessel wall is a critical first step in hemostasis.
- von Willebrand Factor (vWF): This protein is pivotal for platelet adherence. When vessels get injured, they expose subendothelial collagen. Platelets can adhere to this collagen thanks to vWF, which acts as a bridge between the platelets and the exposed collagen.

While other agents like ADP and serotonin are involved in platelet aggregation and Thromboxane A2 in amplifying the aggregation process, it’s the vWF that is essential for the initial adherence of platelets to the injury site.

Question 3

4. Which of the following factors are NOT involved in preventing clot propagation?
   A. Thrombomodulin
   B. Tissue plasminogen activator (tPA) release by the endothelium
   C. Nitric oxide release from the endothelium
   D. APC complexes with protein S

Answer 3

C. Nitric oxide release from the endothelium

4. Preventing Clot Propagation
- Thrombomodulin (TM) on endothelium forms complex with thrombin, deactivating it and activating protein C (APC).
- APC inhibits factors V and VIII, reducing thrombin generation.
- Tissue plasminogen activator (tPA) released from endothelium starts fibrinolysis by converting plasminogen.
- APC increases tPA activity by consuming plasminogen activator inhibitor-1 (PAI-1).
- Tissue factor pathway inhibitor (TFPI) and Antithrombin III (AT-III) also play roles in inhibiting thrombin formation.
- APC complex with protein S is a potent thrombin inhibitor.

The body has mechanisms to prevent excessive clotting or clot propagation:
- Thrombomodulin: It forms a complex with thrombin, rendering thrombin unavailable for further clotting action.
- Tissue Plasminogen Activator (tPA): Released from the endothelium following injury, it aids in fibrinolysis.
- APC-Protein S Complex: This complex inhibits clotting by targeting factors Va and VIIIa.

However, Nitric oxide primarily acts as a vasodilator and doesn’t play a direct role in the feedback inhibition of the coagulation cascade.

Question 3

3. Which of the following clotting factors is the first factor common to both intrinsic and extrinsic pathways?
   A. Factor I (fibrinogen)
   B. Factor IX (Christmas factor)
   C. Factor X (Stewart-Prower factor)
   D. Factor XI (plasma thromboplasma antecedent)

Answer 3

C. Factor X (Stewart-Prower factor)

3. Common Factor in Coagulation Pathways
The coagulation cascade is a series of events involving various clotting factors that lead to clot formation. There are two main pathways:
- Intrinsic Pathway: Initiated usually by trauma within the blood vessel or exposure to collagen. It involves factors XII, XI, IX, and VIII.
- Extrinsic Pathway: Begins when blood comes in contact with tissue factor (TF), like from damaged tissue.

Both pathways converge at Factor X, making it the first common factor for both pathways. The activation of Factor X is the penultimate step before fibrin formation and clot stabilization.

Question 4

5. Which of the following congenital factor deficiency often presents in the first few days of life?
   A. Factor VII
   B. Factor IX
   C. Factor XI
   D. Factor XIII

Answer 4

D. Factor XIII

5. Congenital Factor XIII Deficiency
- Rare autosomal recessive disease with severe bleeding diathesis.
- Clots form normally but are easily broken down due to fibrinolysis.
- Characteristic umbilical stump bleeding and high risk of intracranial bleeding.
- Women with this deficiency usually have spontaneous abortions unless they receive replacement therapy.

5. Congenital Factor Deficiency
Factor XIII deficiency is a rare congenital condition, but it is significant for its severe bleeding tendencies. It presents early in life, often noted due to bleeding from the umbilical stump. The bleeding associated with this deficiency is particularly concerning because it tends to be delayed. While the clot forms initially, it is not stable and is susceptible to breaking down. The treatment involves replacing the missing factor with fresh frozen plasma, cryoprecipitate, or factor XIII concentrate.

Question 5

6. Which of the following is NOT a cause of thrombocytopenia?
   A. Immune thrombocytopenia purpura (ITP)
   B. Hemolytic uremia syndrome (HUS)
   C. B12 deficiency
   D. Clopidogrel administration

Answer 5

D. Clopidogrel administration

6. Causes of Thrombocytopenia
Thrombocytopenia is characterized by a reduced number of circulating platelets. The causes can be categorized based on:
- Failure of production: This can occur due to bone marrow disorders, certain nutrient deficiencies, chemotherapy, radiation, alcohol intoxication, and viral syndromes.
- Shortened platelet survival: Conditions such as ITP, HIT, TTP, and HUS lead to a reduced lifespan of platelets.
- Sequestration: This is when platelets get trapped, usually in an enlarged spleen, due to various underlying conditions.

Clopidogrel doesn’t reduce the number of platelets. Instead, it affects platelet function by inhibiting it, which can lead to a bleeding tendency, but not thrombocytopenia.

Question 6

7. Primary immune thrombocytopenia (ITP):
   A. Occurs more often in children with adults, but has a similar clinical course.
   B. Includes HIT as a subtype of drug-induced ITP.
   C. is also known as thrombotic thrombocytopenic purpura (TTP).
   D. is a disease of impaired platelet production of unknown etiology.

Answer 6

B. Includes HIT as a subtype of drug-induced ITP.

7. Primary Immune Thrombocytopenia (ITP)
- Also known as idiopathic thrombocytopenic purpura.
- Acute onset in children, typically post-viral illness. In adults, it’s chronic with no identifiable cause.
- Pathophysiology involves both impaired platelet production and T cell–mediated platelet destruction.
- HIT is a subtype of drug-induced ITP.

ITP is a condition where the immune system targets and destroys platelets, leading to a reduced number of circulating platelets.
- In children, ITP usually presents acutely, often after a viral illness, and tends to be short-lived.
- In adults, ITP is chronic and idiopathic, meaning it has no identifiable cause.
- HIT is a subtype of drug-induced immune thrombocytopenia, triggered by heparin exposure.
- TTP is a separate condition and is characterized by small blood clots throughout the body, which can lead to serious complications.

Question 7

8. Which of the following is NOT an acquired platelet hemostatic defect?
   A. Massive blood transfusion following Trauma
   B. Acute renal failure
   C. Disseminated intravascular coagulation (DIC)
   D. Polycythemia vera

Answer 7

C. Disseminated intravascular coagulation (DIC)

8. Acquired Platelet Hemostatic Defect
- Impaired platelet function can occur even with a normal platelet count.
- 80% of overall clot strength is linked to platelet function.
- Conditions impairing ADP-stimulated aggregation include massive transfusion, uremia, severe trauma, thrombocythemia, polycythemia vera, and myelofibrosis.
- DIC is characterized by systemic coagulation pathway activation leading to excessive thrombin generation and microthrombi formation.

DIC, however, is not just a platelet defect. It’s a systemic activation of coagulation pathways, which leads to widespread microclots. This is a broader problem than just platelet dysfunction.

Question 8

9. What drug irreversibly inhibits platelet function by irreversible acetylation of platelet prostaglandin synthase?
   A. Aspirin
   B. Clopidogrel
   C. Dipyridamole
   D. Glycoprotein IIB/IIIA inhibitors

Answer 8

A. Aspirin

9. Drugs Inhibiting Platelet Function
9. Drugs Affecting Platelet Function
Several drugs can inhibit platelet function:
- Aspirin: It irreversibly acetylates the platelet prostaglandin synthase, inhibiting the production of thromboxane A2, a promoter of platelet aggregation.
- Clopidogrel and Prasugrel: These inhibit ADP-induced platelet aggregation.
- Dipyridamole: It increases cAMP levels in platelets, inhibiting platelet aggregation.
- GP IIb/IIIa inhibitors: They prevent platelet aggregation by blocking the final common pathway of platelet aggregation.

Question 9

10. Which is TRUE about trauma-induced coagulopathy (TIC)?
    A. The acute coagulopathy of trauma is mechanistically similar to disseminated intravascular coagulation (DIC).
    B. Coagulopathy can develop in trauma patients following acidosis, hypothermia, and dilution of coagulation factors though coagulation is normal on admission.
    C. TIC is caused by shock and tissue injury.
    D. Acute coagulopathy of trauma is mainly a dilutional coagulopathy.

Answer 9

C. TIC is caused by shock and tissue injury.

10. Trauma-Induced Coagulopathy (TIC)
TIC is a coagulopathy that can develop in trauma patients. It’s distinct from other types of coagulopathies:
- It can present upon admission, even before the effects of interventions like fluid resuscitation can manifest.
- It’s precipitated by tissue injury or hemorrhagic shock.
- It’s not merely a dilutional coagulopathy (which would be caused by the addition of large volumes of fluids or blood products).
- It’s different from DIC in its underlying mechanisms and manifestations.

Question 10

11. Warfarin use is often associated with an increased morbidity and mortality in acutely injured and emergency surgery patients, with rapid reversal, these complications can be reduced: Which is NOT TRUE about rapid reversal of warfarin effect?
    A. Vitamin K should be given to sustain the effects of plasma and prothrombin complex concentrate (PCC).
    B. PCC is superior to plasma.
    C. PCC more rapidly corrects INR but is associated with excess thromboembolic events.
    D. Four-factor PCC’s have more reliable correction of INR compared to three-factor PCCs.

Answer 10

B. PCC is superior to plasma.

11. Rapid Reversal of Warfarin Effect
- Warfarin complications can be reduced with rapid reversal in acutely injured and emergency surgery patients.
- Reversal options include vitamin K, plasma, cryoprecipitate, recombinant factor VIIa, and factor concentrates.
- Vitamin K sustains the effects of plasma or PCC due to their short half-lives.
- PCC has a faster reversal speed than plasma and doesn’t risk fluid overload.
- Four-factor PCCs provide a more reliable INR correction than three-factor PCCs.

11. Rapid Reversal of Warfarin Effect
Warfarin, an anticoagulant, poses a risk in surgical patients due to increased chances of bleeding. Rapid reversal is essential to minimize complications.
- Vitamin K sustains the effects of plasma and PCC, ensuring prolonged reversal of warfarin’s effects.
- PCC (Prothrombin Complex Concentrate) is a preparation that contains clotting factors. Though it offers faster reversal than plasma and avoids fluid overload, its cost is higher and doesn’t have fewer adverse events.
- There are two primary types of PCCs: three-factor (containing clotting factors II, IX, and X) and four-factor (containing factors II, VII, IX, and X). The latter has been found to correct INR more reliably.

Question 11

12. What is the best laboratory test for determine degree of anticoagulation with direct oral anticoagulants such as dabigatran and rivaroxaban?
    A. Prothrombin time/International normalized ratio (PT/INR)
    B. Partial thromboplastin time (PTT)
    C. Bleeding time
    D. None of the above

Answer 11

D. None of the above

12. Direct Oral Anticoagulants (DOACs)
- DOACs have no easy method to detect the degree of anticoagulation.
- Idarucizumab, a humanized monoclonal antibody fragment, has been approved for reversing the anticoagulation effects of dabigatran.

Direct Oral Anticoagulants (DOACs) like dabigatran and rivaroxaban have revolutionized anticoagulation therapy. However, there’s no readily available method to detect their degree of anticoagulation. This is concerning, especially in situations where reversal is required.

Question 12

13. A 45-year-old man is now postoperative day 6 after colon resection for perforated diverticulitis, and is noted to have new bruising at venipuncture sites. Platelet count is measured at 45,000 platelets per milliliter. You suspect this is due to Heparin-induced thrombocytopenia (HIT). Which of the following is TRUE?
    A. HIT is due to an antibody against platelet factor 4 (PF4).
    B. This can only occur with full dose unfractionated heparin.
    C. HIT is avoided by using fractionated heparins only.
    D. Anticoagulation with oral warfarin should be initiated immediately.

Answer 12

A. HIT is due to an antibody against platelet factor 4 (PF4).

13. Heparin-induced Thrombocytopenia (HIT)
- HIT is a drug-induced immune thrombocytopenia caused by antibodies against platelet factor 4 (PF4).
- Platelet count drops 5-7 days after starting heparin, but sooner upon reexposure.
- HIT can result from both full-dose unfractionated heparins and low molecular weight heparins.
- HIT is associated with both arterial and venous thrombosis.

Question 13

14. Which findings are not consistent with thrombotic thrombocytopenic purpura (TTP)?
    A. Splenomegaly
    B. Fever
    C. Schistocytes on peripheral blood smear
    D. Platelet activation

Answer 13

D. Platelet activation

14. Thrombotic Thrombocytopenic Purpura (TTP)
- TTP involves inhibition of the enzyme ADAM S13, leading to unrestrained microthrombi growth.
- TTP is characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological symptoms, and renal insufficiency.
- Schistocytes are observed on a peripheral blood smear.
- Plasma exchange with FFP is the primary treatment for acute TTP.

TTP is characterized by small blood clots forming throughout the body due to uncontrolled growth of microthrombi. The disease presents with thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological symptoms, and renal insufficiency. The mainstay treatment is plasma exchange and the use of drugs like Rituximab in refractory cases.

Question 14

15. Which of the following is FALSE regarding coagulation during cardiopulmonary bypass (CPB)?
    A. Contact with circuit tubing and membranes activates inflammatory
    cascades and causes anormal platelet and clotting factor function.
    B. Coagulopathy is compounded by sheer stress.
    C. Following bypass, platelet morphology and ability to aggregate are irreversibly altered.
    D. Coagulopathy is compounded by hypothermia and hemodilution.

Answer 14

C. Following bypass, platelet morphology and ability to aggregate are irreversibly altered.

15. Coagulation During Cardiopulmonary Bypass (CPB)
- In CPB, circuit tubing and membrane contact result in abnormal platelet and clotting factor activation.
- Platelets undergo reversible changes, leading to sequestration in filters, partially degranulated platelets, and platelet fragments.
- This coagulopathy is intensified by shear stress, induced hypothermia, hemodilution, and anticoagulation.

Question 15

16. Which of the following facts about transfusion and crossmatching is FALSE?
    A. Universal donor type O-negative red blood cells and type AB plasma may be transfused to all recipients.
    B. Platelets also require crossmatching.
    C. The administration of Rh-positive red blood cells is acceptable if Rh- negative red blood cells blood is not available.
    D. Crossmatched whole blood may be ideal therapy for resuscitation of trauma patients.

Answer 15

C. The administration of Rh-positive red blood cells is acceptable if Rh- negative red blood cells blood is not available.

16. Transfusion and Crossmatching
- Platelets don’t require crossmatching.
- In emergencies, universal donor type O-negative red blood cells and type AB plasma can be transfused to all recipients. Type A plasma is also increasingly used in emergencies due to its compatibility with a majority of potential recipients.
- Whole blood is ideal for acute traumatic hemorrhagic shock, but its access is limited in many civilian centers.

Blood transfusion is a life-saving intervention, but ensuring compatibility is crucial.
- Universal donor type O-negative red blood cells and type AB plasma: These blood types are considered universal donors and can be given to any patient regardless of their blood type. Using them in emergencies ensures immediate availability and safety.
- Platelet crossmatching: Unlike red blood cells, platelets don’t require crossmatching. This is because platelet transfusion reactions are rare and are typically non-hemolytic.
- Whole blood for trauma: The use of whole blood, which contains all components of blood, is considered ideal for resuscitating trauma patients due to its comprehensive nature. It’s not just the volume but also the components of the blood that are replaced.

Question 16

17. Following recent abdominal surgery, your patient is admitted to the ICU with septic shock. Below what level of hemoglobin would a blood transfusion be indicated?
    A. <12 g/dL
    B. <10 g/dL
    C. <8 g/dL
    D. <7 g/dL

Answer 16

D. <7 g/dL

17. Transfusion Indications in ICU Patients
- A hemoglobin level of less than 10 g/dL or hematocrit level <30% no longer automatically indicates a need for preoperative red blood cell transfusion.
- Maintaining hemoglobin levels between 7 and 9 g/dL in critically ill patients does not adversely affect mortality.
- Patient-specific characteristics and the overall clinical context should be considered when deciding on RBC transfusions in non-acutely hemorrhaging patients.

In critically ill patients, especially after surgery, the decision to transfuse is based not just on the hemoglobin level but also on the overall clinical picture.
- A hemoglobin level of less than 7 g/dL is generally considered a threshold for transfusion in ICU patients without acute bleeding. Transfusing at higher hemoglobin levels might not confer additional benefit and might expose patients to unnecessary risks associated with transfusion.

Question 17

18. Which of the following is not part of damage control resuscitation (DCR)?
    A. Permissive hypotension
    B. Resuscitating with large volumes of crystalloid to limit RBC transfusion
    C. Immediate release and administration of a predefined ration of blood products to mimic whole blood
    D. Use of hemostatic adjuncts

Answer 17

B. Resuscitating with large volumes of crystalloid to limit RBC transfusion

18. Damage Control Resuscitation (DCR)
- DCR involves an early approach to managing the exsanguinating patient.
- The components of DCR include permissive hypotension, minimizing crystalloid-based resuscitation, administering predefined balanced blood products immediately, and using hemostatic adjuncts.
- The PROPPR trial highlighted the advantages of a 1:1:1 ratio of plasma to platelets to RBCs, showing decreased mortality due to hemorrhage at 24 hours.

18. Damage Control Resuscitation (DCR) in Trauma
DCR is an approach in trauma care that focuses on rapid control of bleeding and optimal resuscitation.
- Permissive hypotension: This strategy allows for a slightly lower blood pressure than normal to reduce bleeding while ensuring vital organs get enough blood supply.
- Minimizing crystalloid: Excessive use of crystalloid solutions (like saline) can dilute blood and impair clotting. DCR focuses on using blood products earlier.
- Predefined blood products: DCR promotes the use of balanced blood products in ratios similar to whole blood. This provides a more physiologic and effective resuscitation.
- Hemostatic adjuncts: These are agents that promote clotting and control bleeding.

Question 18

19. In patients with significant blood loss, which of the following is incorrect?
    A. Resuscitation with whole blood
    B. Resuscitation with packed red blood cells, platelet, and FFP in a 1:1:1 ratio
    C. Packed red blood cells with transfusion of FFP and platelets as needed (when the measured INR > 2 and PLT# is <75,000)
    D. Resuscitation with crystalloid and artificial colloid to avoid transfusion reactions until hemorrhage is controlled.

Answer 18

C. Packed red blood cells with transfusion of FFP and platelets as needed (when the measured INR > 2 and PLT# is <75,000)

19. Blood Loss Resuscitation
- The PROPPR trial showcased the benefits of resuscitating with packed red blood cells, platelets, and plasma in a 1:1:1 ratio.
- Whole blood transfusion has similar outcomes since it inherently contains plasma and platelets in similar ratios.
- Waiting for INR and platelet count to dictate transfusion strategies can delay achieving hemostasis.

After significant blood loss, the focus is on replacing the lost volume and ensuring effective clotting.
- Whole blood resuscitation: This replaces all components of blood and is similar to the body’s natural composition.
- Balanced blood products: Using red blood cells, plasma, and platelets in a balanced ratio mimics whole blood and is found to be effective in trauma resuscitation.
- Avoiding excessive crystalloids: Excessive use of crystalloids can impair clotting and should be avoided.

Question 19

20. Less than 0.5% of transfusions result in a serious transfusion-related complication. Which of the following is the leading cause of transfusion-related deaths?
    A. Transfusion-related acute lung injury (TRALI)
    B. ABO hemolytic transfusion reactions
    C. Bacterial contamination of platelets
    D. Iatrogenic hepatitis C: infection

Answer 19

A. Transfusion-related acute lung injury (TRALI)

20. Transfusion-related Complications
- Serious complications from transfusions are rare, occurring in less than 0.5% of cases.
- Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related deaths.

20. Transfusion-Related Complications
While blood transfusion is a life-saving measure, it is not without risks.
- Transfusion-related acute lung injury (TRALI): This is a severe pulmonary reaction following transfusion and is now recognized as the leading cause of transfusion-related death. It results from an immune reaction that causes lung inflammation and damage.
- ABO hemolytic reactions: Transfusing blood of the wrong ABO type can cause a severe and sometimes fatal reaction. This is why crossmatching and ensuring the correct blood type is crucial.
- Bacterial contamination: Blood products can sometimes be contaminated with bacteria, leading to septic reactions in recipients.
- Iatrogenic infections: Transfusions can sometimes transmit infections like hepatitis, though the risk is now very low due to rigorous testing and screening of blood products.

Question 20

21. TRALI does not include:
    A. Transfusion-related circulatory overload (TACO). B. Noncardiogenic pulmonary edema.
    C. Fever and rigors.
    D. Bilateral pulmonary infiltrates.

Answer 20

A. Transfusion-related circulatory overload (TACO).

21. TRALI (Transfusion-Related Acute Lung Injury)
- TRALI is defined as noncardiogenic pulmonary edema related to transfusion and can happen with any plasma-containing blood product.
- Symptoms of TRALI include dyspnea, hypoxemia, fever, rigors, and bilateral pulmonary infiltrates seen on chest X-ray.
- TRALI usually occurs within 1 to 2 hours of the transfusion start but always before 6 hours.
- Its incidence has decreased with reduced transfusion of plasma from female donors. It usually resolves with supportive therapy.
- Another condition, Transfusion-related circulatory overload (TACO), can occur with rapid infusion and is avoidable, especially in older patients with underlying heart disease.

Question 21

22. Diseases that are not generally transmitted by blood transfusion include:
    A. Malaria, Chagas’ disease.
    B. CMV, hepatitis C, and HIV.
    C. Zika and West Nile Virus.
    D. All of the above.

Answer 21

A. Malaria, Chagas’ disease.

22. Diseases Transmitted by Transfusion
- Transfusion can transmit diseases like Malaria, Chagas’ disease, and brucellosis.
- The risk of transmitting hepatitis C and HIV-1 has been significantly reduced due to better screening methods.
- Concerns about the transmission of other pathogens like West Nile virus have led to trials of “pathogen inactivation systems” to reduce infectious levels.
- The Zika virus has also been a concern, with transmission cases reported in Brazil.

Question 22

23. What are the uses of thromboelastography (TEG)?
    A. Predicting the need for lifesaving interventions after resuscitation for trauma
    B. Predicting 24-hour and 30-day mortality following trauma
    C. Predicting early transfusion of RBC, plasma, platelet, and cryoprecipitate
    D. All of the above

Answer 22

D. All of the above

23. Thromboelastography (TEG)
- TEG is valuable in predicting early transfusion needs, the necessity for life-saving interventions after trauma, and mortality outcomes.
- Some centers use TEG instead of traditional coagulation tests for evaluating injured patients in the emergency department due to its association with clinical outcomes.

Question 23

24. Which of the following is TRUE in a thromboelastography (TEG) tracing?
    A. The r-value represents the clotting factor activity and initial fibrin formation and is increased with factor deficiency or severe hemodilution.
    B. K time is prolonged with hypofibrinogenemia and significant factor deficiency.
    C. Decreased (alpha) or angle is treated with cryoprecipitate transfusion or fibrinogen administration.
    D. All of the above.

Answer 23

D. All of the above.

24. TEG Tracing Parameters
- The r-value (reaction time) in TEG represents clotting factor activity and initial fibrin formation. It increases with factor deficiency or severe hemodilution.
- The k-time (clot kinetics) represents interactions of clotting factors and platelets. It’s prolonged with hypofibrinogenemia and factor deficiency.
- The alpha or angle ( ) reflects clot acceleration and interactions of clotting factors and platelets.
- The maximal amplitude (mA) represents clot strength and is influenced by platelet function and fibrinogen levels.
- The G-value is a measure derived from the mA value and reflects overall clot strength. An increased G-value indicates hypercoagulability, while a decrease indicates hypocoagulable states.
- The LY30 represents clot stability and the presence of increased fibrinolysis.

Question 24

1. Which of the following is NOT one of the four major physiologic events of hemostasis?
   A. Fibrinolysis
   B. Vasodilatation
   C. Platelet plug formation
   D. Fibrin production

Answer 24

B. Vasodilatation

1. Four Major Physiologic Events of Hemostasis
Hemostasis is an intricate mechanism that primarily aims to halt blood loss from a wounded vessel. The process incorporates:

• Vascular Constriction: As a direct response to injury, vessels constrict to reduce blood flow, acting as the first line of defense against hemorrhage.
• Platelet Plug Formation: When vessels are injured, platelets adhere to the exposed site. The platelets then release chemicals that attract even more platelets to the site and they stick together (aggregation). This forms a temporary “platelet plug” that covers the break in the vessel wall.
• Fibrin Formation: The coagulation cascade is activated, leading to the conversion of fibrinogen to fibrin threads that weave through the platelet plug, solidifying and stabilizing it into a more durable clot.
• Fibrinolysis: After the vessel heals, the clot must be removed. The fibrinolytic system dissolves the clot by converting plasminogen to plasmin, which digests fibrin and dissolves the clot.

Vasodilatation isn’t a primary event in hemostasis. Instead, vasoconstriction is the immediate response to vascular injury, helping to reduce blood loss.

Question 25

2. Which is required for platelet adherence to injured endothelium?
   A. Tromboxane A2
   B. Glycoprotein (GP) IIb/Illa
   C. Adenosine diphosphate (ADP)
   D. Von Willebrand factor (vWF)

Answer 25

D. Von Willebrand factor (vWF)

2. Platelet Adherence to Injured Endothelium
The process by which platelets adhere to the exposed subendothelial collagen of an injured vessel is crucial to initiating hemostasis. Key points include:

• von Willebrand Factor (vWF): This is a crucial protein in the blood that helps platelets stick to the site of a wound. In the absence of vWF, as seen in individuals with von Willebrand’s disease, this initial platelet adhesion process is disrupted.
• Glycoproteins: Platelets use glycoproteins on their surface to adhere to the vWF. Specifically, vWF binds to glycoprotein (GP) I/IX/V on the platelet membrane.
• ADP and Serotonin: After the adhesion, platelets release ADP and serotonin, which play pivotal roles in recruiting more platelets to the site of injury, ultimately forming a platelet plug.

Question 26

3. Which of the following clotting factors is the first factor common to both intrinsic and extrinsic pathways?
   A. Factor I (fibrinogen)
   B. Factor IX (Christmas factor)
   C. Factor X (Stuart-Prower factor)
   D. Factor XI (plasma thromboplasma antecedent)

Answer 26

C. Factor X (Stuart-Prower factor)

3. Coagulation Pathways
The clotting process in the body comprises of two main pathways:

• Intrinsic Pathway: This is initiated when blood comes into contact with a foreign surface, like a negatively charged surface. It involves factors XII, XI, IX, and VIII.
• Extrinsic Pathway: Triggered by tissue injury, this pathway begins with the release or exposure of tissue factor (TF) on the endothelium. TF binds to factor VII, facilitating its activation.

Both pathways converge at the activation of factor X (hence it’s common to both), leading to the culmination of the coagulation cascade, which results in the formation of fibrin, and subsequently, a stable clot.

Question 27

4. Which congenital factor deficiency is associated with delayed bleeding after initial hemostasis?
   A. Factor VII
   В. Factor IX
   C. Factor XI
   D. Factor XIII

Answer 27

D. Factor XIII

4. Congenital Factor XIII Deficiency
- Factor XIII deficiency is a rare autosomal recessive disease with a severe bleeding diathesis.
- Bleeding is usually delayed because initial clots form but are susceptible to fibrinolysis.
- Umbilical stump bleeding is common, and there’s a high risk of intracranial bleeding.
- Women with this deficiency tend to experience spontaneous abortion unless they receive replacement therapy.
- Treatment can be with fresh frozen plasma, cryoprecipitate, or a Factor XIII concentrate.

Discussion: Factor XIII deficiency is especially noteworthy due to its unique presentation. Unlike other clotting disorders where bleeding might be immediate, in Factor XIII deficiency, the initial clot forms normally but is not stable and can break down easily, leading to delayed bleeding. This can have significant clinical implications, especially in trauma or surgical settings.

Question 28

5. In a previously unexposed patient, when does the platelet count fall in heparin-induced thrombocytopenia (HIT)?
   A. <24 hours
   B. 24-28 hours
   C. 3-4 days
   D. 5-7 days

Answer 28

D. 5-7 days

5. Heparin-induced Thrombocytopenia (HIT)
- HIT results from antibodies against platelet factor-4 formed during exposure to heparin.
- It leads to platelet activation and endothelial function disturbances, causing thrombocytopenia and intravascular thrombosis.
- Typically, the platelet count drops 5-7 days after starting heparin. If re-exposed, the drop can occur within 1-2 days.

Discussion: HIT is a critical consideration for patients on heparin therapy. The immune response against platelet factor-4 not only reduces the platelet count but also predisposes to clot formation, creating a paradoxical scenario of bleeding and clotting risks in the same patient.

Question 29

6. Which is NOT an acquired platelet hemostatic defect?
   A. Massive blood transfusion following trauma
   B. Acute renal failure
   C. Disseminated intravascular coagulation (DIC)
   D. Polycythemia vera

Answer 29

C. Disseminated intravascular coagulation (DIC)

6. Acquired Platelet Hemostatic Defect
- Platelet function is crucial for clot strength.
- Massive blood transfusion impairs ADP-stimulated platelet aggregation.
- Uremia (seen in kidney failure) can lead to increased bleeding time and impaired platelet aggregation.
- Conditions like thrombocythemia, polycythemia vera, and myelofibrosis also have defective platelet aggregation.
- DIC is characterized by systemic coagulation activation causing excessive thrombin generation and widespread microthrombi.

Discussion: Platelets play a pivotal role in hemostasis, and their dysfunction can lead to significant bleeding complications. Numerous conditions and situations can impair platelet function, from kidney diseases to certain blood disorders and massive transfusions. Understanding these can guide therapeutic decisions, especially in bleeding patients.

Question 30

7. What is true about coagulopathy related to trauma?
   A. Acute coagulopathy of trauma is mechanistically similar to DIC.
   B. Coagulopathy can develop in trauma patients following acidosis, hypothermia, and dilution of coagulation factors, though coagulation is normal upon admission.
   C. Acute coagulopathy of trauma is caused by shock and tissue injury.
   D. Acute coagulopathy of trauma is mainly a dilutional coagulopathy.

Answer 30

C. Acute coagulopathy of trauma is caused by shock and tissue injury.

7. Trauma-related Coagulopathy
- Traditional understanding attributed trauma-related coagulopathy to factors like acidosis, hypothermia, and dilution of coagulation factors.
- Recent data reveals that over a third of injured patients show evidence of coagulopathy upon admission.
- Such patients have a higher risk of mortality, especially in the first 24 hours post-injury.
- The coagulopathy isn’t merely dilutional but is complex with multiple underlying mechanisms.
- The primary initiators for this coagulopathy are shock and tissue injury.
- This coagulopathy is distinct from DIC and has its unique components of hemostatic failure.

Discussion: Trauma patients often present a challenge in terms of coagulation. While the traditional understanding linked coagulopathy to factors like acidosis, recent insights suggest an inherent coagulopathy in a significant subset of trauma patients. Recognizing and managing this can be pivotal in improving outcomes in trauma care.

Question 31

8. What is the best laboratory test for determine degree of anticoagulation with dabigatran and rivaroxaban?
   A. Prothrombin time/international normalized ratio
   (PT/INR)
   B. partial thromboplastin time (PTT)
   C. Bleeding time
   D. None of the above

Answer 31

D. None of the above

8. Anticoagulation with Dabigatran and Rivaroxaban

Dabigatran and rivaroxaban lack a readily available method to determine the degree of anticoagulation.
They do not have an available reversal agent.
The nonreversible coagulopathy associated with these drugs is concerning for emergency care providers.

Newer anticoagulants, such as dabigatran and rivaroxaban, have no readily available method of detection of the degree of anticoagulation. More concerning is the absence of any available reversal agent. Unlike war farin, the nonreversible coagu-lopathy associated with dabigatran and rivaroxaban is of great concern to those providing emergent care to these patients.

Question 32

9. A fully heparinized patient develops a condition requiring emergency surgery. After stopping the heparin, what else should be done to prepare the patient?
   A. Nothing, if the surgery can be delayed for 2 to 3 hours.
   B. Immediate administration of protamine 5 mg for every 100 units of heparin most recently administered.
   C. Immediate administration of FFP.
   D. Transfusion of 10 units of platelets.

Answer 32

A. Nothing, if the surgery can be delayed for 2 to 3 hours.

9. Emergency Surgery in Heparinized Patients
- Discontinue heparin as the first step.
- Protamine sulfate can be used for rapid reversal.
- Adverse reactions can occur with protamine, especially in patients with fish allergies.
- Protamine might have its anticoagulant effect.
- For elective surgery in patients on coumarin-derivative therapy, stopping the drug several days before the operation and checking the prothrombin concentration is the standard approach.

Discussion:
Emergency surgeries in patients who are anticoagulated pose a unique challenge. Heparin, a commonly used anticoagulant, can be reversed rapidly using protamine sulfate. However, the administration of protamine is not without risks. Significant adverse reactions can arise, especially in individuals with allergies to fish. Furthermore, protamine itself might exhibit anticoagulant properties, which can complicate the situation further. In patients undergoing elective surgeries and are on coumarin derivatives (another class of anticoagulants), the standard approach is to halt the medication several days prior to the operation and ensure safe prothrombin levels.

Question 33

10. Primary ITP
    A. Occurs more often in children than adults, but has a similar clinical course.
    B. Includes HIT as a subtype of drug-induced ITP.
    C. Is also known as thrombotic thrombocytopenic pur-pura (TTP).
    D. Is a disease of impaired platelet production, unknown cause.

Answer 33

B. Includes HIT as a subtype of drug-induced ITP.

10. Primary Immune Thrombocytopenia (ITP)
- ITP in children usually follows a viral illness, is acute, and short-lived.
- ITP in adults is typically chronic, has a gradual onset, and lacks an identifiable cause.
- ITP platelets are young and functional, leading to less bleeding for a given count than if there’s a failure in platelet production.
- ITP involves impaired platelet production and T cell-mediated platelet destruction.
- Treatment for drug-induced ITP might involve stopping the drug, and other interventions like corticosteroids, gamma globulin, or anti-D immunoglobulin.
- Heparin-induced thrombocytopenia (HIT) is a subtype of drug-induced ITP.

Discussion:
Primary immune thrombocytopenia (ITP) is a hematological disorder with different presentations in children and adults. While children often develop ITP after a viral infection and it’s usually short-lived, adults typically experience a more chronic form without a clear triggering event. An interesting aspect of ITP is that the circulating platelets are relatively young and highly functional. This means that patients with ITP may not bleed as much as those with other conditions leading to low platelet counts. The underlying mechanism involves a combination of decreased platelet production and increased destruction, mediated by the immune system. Drug-induced ITP is a related condition, and its management might require stopping the offending drug. Additionally, medications like corticosteroids or gamma globulin can be beneficial. A notable subtype of drug-induced ITP is heparin-induced thrombocytopenia (HIT), which arises due to an immunological reaction following exposure to heparin.

Question 34

11. Which of the following is the most common intrinsic platelet defect?
    A. T rombasthenia
    B. Bernard-Soulier syndrome
    C. Cyclooxygenase deficiency
    D. Storage pool disease

Answer 34

D. Storage pool disease

Intrinsic Platelet Defect - Storage Pool Disease
- Storage pool disease is the most common intrinsic platelet defect.
- It can involve deficiencies in either dense granules or α-granules or both.
- Dense granule deficiency is most common and can be an isolated defect or associated with partial albinism in the Hermansky-Pudlak syndrome.
- Reduced ADP release from these platelets primarily causes bleeding.
- The isolated defect of α-granules gives platelets a gray appearance, termed the gray platelet syndrome.
- Treatment includes DDAVP for mild bleeding, and platelet transfusion is required for severe cases.

Discussion:
Storage pool disease affects the granules within platelets, where essential substances for the clotting process are stored. The dense granules contain crucial elements like ADP and calcium. When these granules are deficient, the platelets cannot release enough ADP, leading to bleeding. The α-granules, on the other hand, store proteins that are essential for platelet function. The gray platelet syndrome, where these granules are missing, typically results in milder bleeding. Interestingly, certain medications like DDAVP can help manage bleeding in these patients, probably because it raises plasma levels of von Willebrand factor, compensating for the platelet defect.

Question 35

12. Which finding is not consistent with TTP?
    A. Microangiopathic hemolytic anemia
    B. Schistocytes on peripheral blood smear
    C. Fever
    D. Splenomegaly

Answer 35

D. Splenomegaly

Thrombotic Thrombocytopenic Purpura (TTP)
- Large von Willebrand factor (vWF) molecules activate platelets in TTP.
- TTP stems from the inhibition of ADAMTS13 enzyme, responsible for cleaving large vWF molecules.
- It presents with thrombocytopenia, microangiopathic hemolytic anemia, fever, renal, and neurologic signs/symptoms.
- Schistocytes on a peripheral blood smear aid in diagnosis.
- Plasma exchange with FFP replacement is the main treatment, and rituximab is promising as an immunomodulatory therapy.

Discussion:
TTP is a disorder where unusually large von Willebrand factor molecules cause platelet activation. These abnormal molecules arise due to the inhibition of an enzyme, ADAMTS13, which usually breaks them down. The hallmark features of TTP include low platelet counts, specific forms of anemia, fever, and symptoms involving the kidneys and nervous system. The appearance of schistocytes (fragmented red blood cells) on blood smears aids in the diagnosis. Treatment involves plasma exchange, where the patient’s plasma containing the large vWF molecules is replaced with fresh frozen plasma. Rituximab, an immunomodulatory drug, shows promise in treating this condition, especially in cases where TTP results from an autoimmune process.

Question 36

13. What is FALSE regarding coagulation during cardiopulmonary bypass (CPB)?
    A. Contact with circuit tubing and membranes activates infammatory cascades, and causes abnormal platelet and clotting factor function.
    B. Coagulopathy is compounded by sheer stress.
    C. Following bypass, platelets’ morphology and ability to aggregate are irreversibly altered.
    D. Coagulopathy is compounded by hypothermia and hemodilution.

Answer 36

C. Following bypass, platelets’ morphology and ability to aggregate are irreversibly altered.

Coagulopathy in Cardiopulmonary Bypass (CPB)
- CPB causes abnormal platelet and clotting factor activation.
- The coagulation system gets disrupted due to contact with circuit tubing and membranes during CPB.
- Platelets undergo reversible changes and may get trapped in the filter, leading to a reduced number of functional platelets.
- The coagulation system’s balance is further disrupted by shear stress, hypothermia, hemodilution, and anticoagulation during CPB.

Discussion:
Cardiopulmonary bypass is an essential technique in cardiac surgeries, but it brings with it a host of challenges related to blood coagulation. The machinery involved, specifically the tubing and membranes, can activate platelets and clotting factors inappropriately. The platelets themselves undergo changes during the process, making them less functional and prone to getting trapped in the system’s filter. Other factors during surgery, like the stress exerted on the blood, cooling of the patient (hypothermia), diluting the blood, and the use of anticoagulants, all contribute to a coagulopathy that can pose bleeding risks for the patient.

Question 37

14. Following a recent abdominal surgery, your patient is in the ICU with septic shock. Below what level of hemoglobin would a blood transfusion be indicated?
    A. <12 g/dL
    B. <10 g/dL
    C. <8 g/dL
    D. <7 g/dL

Answer 37

D. <7 g/dL

Question 38

15. Less than 0.5% of transfusions result in a serious transfusion-related complication. What is the leading cause of transfusion-related deaths?
    A. Transfusion-related acute lung injury
    B. ABO hemolytic transfusion reactions
    C. Bacterial contamination of platelets
    D. Iatrogenic hepatitis C infection

Answer 38

A. Transfusion-related acute lung injury

Question 39

16. Allergic reactions do not occur with
    A. Packed RBCs
    B. FFP
    C. Cryoprecipitate
    D. None of the above

Answer 39

D. None of the above

Question 40

17. What is the risk of Hepatitis C and HIV-1 transmission with blood transfusion?
    A. 1:10,000,000
    B. 1:1,000,000
    C. 1:500,000
    D. 1:100,000

Answer 40

B. 1:1,000,000

Question 41

18. What is NOT a cause of bleeding due to massive transfusion?
    A. Dilutional coagulopathy
    B. Hypofibrinogenemia
    C. Hypothermia
    D. 2,3-DPG toxicity