Principles hematology

Question 1

Three layers of the vessel wall

Answer 1

Intima: Inner, primarily endothelial cells

Media: middle subendothelial, contains collagen and bibronectin

Adventitia: outer, Controls blood flow by influencing the vessel’s degree of contraction

Question 2

Procoagulants

Answer 2

Coagulation factors, collagen, vWF, protein C, protein S, fibronectin, thrombomodulin

Question 3

Anticoagulant

Answer 3

antithrombin III

Question 4

Vasodilation

Answer 4

nitric oxide
prostacyclin

Question 5

vasoconstriction

Answer 5

thromboxane A2
ADP
serotonin

Question 6

fibrinolytic

Answer 6

plasminogen
tPA
urokinase

Question 7

antifibrinolytic

Answer 7

plasminogen activator inhibitor

Question 8

Stages of vessel injury

Answer 8

The vessel wall immediately contracts to cause a tamponade, thereby decreasing blood flow

The area adjacent to the injury vasodilates and distributes blood to the surrounding organs and tissues

Contraction is followed by three separate stages in the formation of a primary plug:
1. adhesion (vWF)
2. activation
3. aggregation

Question 9

What are the two separate pathways of the clotting cascade?

Answer 9

extrinsic and intrinsic

Question 10

Extrinsic (tissue factor) pathway

Answer 10

Activated by release of tissue factor (TF) when damage occurs outside the vessel wall (i.e., organ trauma, crushing injury)

TF (factor III) activates proconvertin (factor VII) changing it to activated factor VII (VIIa)
Once activated, factor VII activates factor X (Stuart-Prower) of the common pathway
Factor X forms a complex with factor V (proaccelerin, a prothrombinase complex), activating factor II (prothrombin), which when activated becomes factor IIa (prothrombin)
Thrombin then activates factor I (fibrinogen) to form activated factor I (Ia, fibrin)

Question 11

Clotting pathway

Question 12

Intrinsic pathway (Contact activation pathway)

Answer 12

Initiated when damage occurs to the blood vessels themselves

Initiated by prekallikrein, high-molecular-weight kininogen (HMWK) , and by the activation of XII (Hageman)

With the help of calcium (factor IV), the coagulation pathways initiates a domino effect

Once activated, each factor activates its subsequent factor.

Factor XII activates factor XI, which activates factor IX, which then activates factor VIII, and ultimately merges at the common pathway and activates factor X. The result is the generation of fibrin from the activation of prothrombin to thrombin.

Question 13

What factors does thrombin assist with?

Answer 13

activating factors V, VIII, I, and XIII

Influences platelet recruitment to the site of injury

Question 14

Common Pathway

Answer 14

The terminal pathway of the coagulation cascade

Factor X has been activated by the extrinsic and intrinsic pathways

Factor X requires factor V (proaccelerin) and calcium to convert factor II (prothrombin) to its active-state thrombin (IIa)

Thrombin then activates factor I (fibrinogen)to its active form Ia (fibrin)

Factor XIII (fibrin-stabilizing factor) is required for the platelet plug to hold. It forms a cross-linked mesh within the platelet plug, increasing its strength.

Fibrin (factor Ia) and factor XIII secure a stable secondary plug and bleeding stops

Once a clot is made, it retracts, eliminating its serum

As the clot retracts, it weaves the edges of the vessel together, healing the injury

Question 15

All the clotting factors and their names

Answer 15

Question 16

What is fibrinolysis regulated by?

Answer 16

Fibrinolysis is regulated by plasma proteins

Question 17

What does the Fibrinolytic System do?

Answer 17

Degrades fibrin once the hemostatic plug is no longer needed

Thrombin, which originally acted as a procoagulant, now acts as an anticoagulant and activates additional anticoagulant mediators

Question 18

Which pathway do PT and aPTT go with?

Answer 18

PT - extrinsic

aPTT - intrinsic

normal PT 12-14 seconds
normal PTT 25-32 seconds
normal ACT 50-150

Question 19

Platelet Infusion Guidelines

Answer 19

**Recommended dose: 1 plateletpheresis pack per 10 kg of body weight. This dose should increase the platelet count by 5,000 to 10,000 mm

Platelet transfusion even with a normal or absent platelet count if there is known or suspected platelet dysfunction

In surgical and obstetric patients, platelet transfusion is rarely indicated if platelet count is > 100,000 μL. Transfusion is indicated for platelet count < 50,000 μL

Normal lifespan: 7 to 10 days
Donated platelet lifespan: 4 to 5 days

Question 20

Fresh Frozen Plasma Infusion Guidelines

Answer 20

*Contains all the clotting factors and naturally occurring inhibitors

Does not provide platelet replacement

Must be ABO compatible

Average FFP volume: 200 to 250 mL

Correction of excessive microvascular bleeding in the presence of an INR > 2.0 and the absence of heparin

Correction of excessive microvascular bleeding secondary to coagulation factor deficiency in patients transfused with more than one blood volume (approximately 70 mL/kg) and when PT/INR and an APTT cannot be obtained

Urgent reversal of warfarin therapy when prothrombin complex concentrate (PCC) is not available

Correction of a known coagulation factor deficiency for which specific concentrates are unavailable

FFP NOT indicated for:
PT/INR and APTT normal
Solely for increasing albumin level or plasma volume

Question 21

Cryoprecipitate Infusion Guidelines

Answer 21

The precipitate collected off the top of FFP as it thaws

Rich in factors VIII, XIII, and fibronectin

Fibrinogen concentration < 80 to 100 mg/dL in the presence of bleeding

An adjunct in massively transfused patients where a fibrinogen level is not obtainable

Patients with congenital fibrinogen deficiencies

Rarely indicated if fibrinogen concentration is > 150 mg/dL

Question 22

Transfusion Guidelines

Answer 22

Few fixed guidelines for transfusion

Guidelines vary by institution

Hgb < 7g/dL is recommended for high-risk patients

Alternatives to PRBC transfusion:
- Preoperative autologous donation
- Acute normovolemic hemodilution
- Blood cell salvage
- Recombinant factor VII

Used to treat hemophilia A (factor VIII) and B (factor IX), inhibitor disorders of factors VIII and IX, factor VII deficiency, and as a universal hemostatic agent
Use cautiously in patients with a history of thrombosis

Question 23

How much does 1 unit of prbc’s (350ml) increase hemoglobin by?

Answer 23

by 1g/dL

Question 24

How much does 1 unit of platelets (250 ml) increase platelets by?

Answer 24

30,000-60,000

Question 25

Von Willebrand Disease (vWD):

Answer 25

Rare bleeding disorder Can be inherited or acquired (secondary to cardiovascular, malignant, or immunologic diseases)

Question 26

Von Willebrands treatment options

Answer 26

Desmopressin, high-dose IV immunoglobulins, FVIII/vWF concentrates, plasma exchange Type 1: desmopressin Type 2 and 3: require vWF concentrate administration Tranexamic acid is also an important adjunctive therapy as either

Question 27

Hemophilia A is a Factor _____ deficiency Hemophilia B is a Factor _____ deficiency

Answer 27

Hemophilia A: Factor VIII deficiency Hemophilia B: Factor IX deficiency

Question 28

Hemophilia symptoms

Answer 28

Spontaneous bleeding Muscle hematomas Joint pain

Question 29

Treatment for hemophilia

Answer 29

Desmopressin Factor VII

Question 30

Perioperative Management of the Hemophilic Patient:

Answer 30

Preoperative assessment of inhibitor screening and inhibitor assay completed within 1 week of surgery Elective procedures early in the day Desmopressin is ok for hemophilia A but of no use in hemophilia B because it does not affect factor 9. Cryo preferred over ffp for A Treatment with viral inactivated plasma-derived or recombinent concentrates is preferred over cryo or ffp.

Question 31

Disseminated Intravascular Coagulation (DIC):

Answer 31

A result of intravascular coagulation activation with microvascular thrombi formation, which causes thrombocytopenia and clotting factors depletion, leading to bleeding and end-organ complications Systemic coagulation activation results in intravascular fibrin deposits, thrombotic microangiography, compromised blood supply to organs, and multiorgan system failure

Question 32

DIC diagnosis

Answer 32

Laboratory tests: platelet count, aPTT, PT, fibrin-related markers (fibrin degradation products, D-dimer), fibrinogen, and antithrombin International Society of Thrombosis and Hemostasis (ISTH) developed a DIC scoring system (score > 5 overt DIC, < 5 suggestive but not affitmative of nonovert DIC)

Question 33

Treatment of DIC

Answer 33

Depends on the underlying condition Identify and eliminate the underlying cause No treatment if mild, asymptomatic, and self-limited Obstetrics: DIC many resolve with prompt delivery of the fetus Sepsis: antibiotics Platelets, FFP, cryoprecipitate Antithrombotics are controversial

Question 34

Sickle Cell Disease

Answer 34

Common, hereditary hemoglobinopathy An autosomal recessive genetic abnormality of the β-globin that codes for production of variant hemoglobin, hemoglobin S Hemoglobin SS Hemoglobin SC Hemoglobin SB- (Beta) thalassemia Beta-zero thalassemia

Question 35

Sickle Cell Disease: Intraoperative Management

Answer 35

Adequate hydration avoid hypoxemia maintain normothermia they have LOTS OF PAIN caution using vasoocclusive devices like tournaquets for patients with pulmonary disease, maybe decrease hemoglobin S level to below 30%

Question 36

Heparin-Induced Thrombocytopenia (HIT):

Answer 36

An immune response to heparin that can progress to severe thrombosis, amputation, and death Suspect HIT when a patient receiving heparin experiences a 50%+ drop in platelet count

Question 37

Clinical presentation of HIT

Answer 37

thrombocytopenia, resistance to heparin anticoagulation, thrombosis, and positive assay tests indicative of HIT

Question 38

Gold standard DIAGNOSIS OF hit

Answer 38

C-serotonin release assay

Question 39

Treatment of HITBased on clinical presentation and laboratory findings Stop heparin immediately Administer direct thrombin inhibitors (argatroban or lepirudin) Prompt surgical intervention for thrombosis that compromises peripheral perfusion

Question 40

Type 1 HIT vs Type 2 HIT

Answer 40

Type I: Thrombocytopenia is mediated by direct heparin-induced platelet aggregation (e.g., nonimmune mediated) * Onset is typically 1 to 4 days after start of heparin therapy * Mild thrombocytopenia (e.g., less than 100,000 per microliter) * Thrombocytopenia often resolves spontaneously even with continued administration of heparin * Typically occurs with high-dose heparin administration * Not associated with thrombosis and serious clinical sequelae

Question 41

Type 1 HIT vs Type 2 HIT

Answer 41

Type II: * Thrombocytopenia is mediated by the actions of the heparin, platelet factor 4, and immunoglobulin G expression (e.g., immune mediated) * Onset is typically 5 to 14 days after start of heparin therapy * Severe thrombocytopenia (e.g., less than 60,000 per microliter) * Thrombocytopenia does not resolve spontaneously, therefore heparin administration must be discontinued * Occurs with any heparin dose and route * Associated with thrombosis and serious clinical sequelae

Question 42

Differences type 1 and type 2 HIT

Answer 42

Type 2 takes longer to develop, is worse, is immune mediated, severe thrombocytopenia, and occur with any dose or route

Question 43

slide 33

Answer 43

slide 33

Question 44

Additional Risk Factors for Acute coronary Stent Thrombosis

Answer 44

Site of stent placement (e.g., bifurcation stenting, side branch occlusion) Left main coronary artery stent Long stent length (greater than 18 mm) Ostial stenting Overlapping stents Placement of multiple stents Small stent diameter (less than 3 mm) Suboptimal stent placement

Question 45

Patient risk factors for coronary stents

Answer 45

Patient Risk Factors: Advanced age Diabetes mellitus Gene polymorphism Hypercoagulable states (e.g., diabetes, malignancy, and surgery) Major cardiac adverse event within 30 days of percutaneous cardiac intervention Reduced left ventricular ejection fraction Prior brachytherapy Renal insufficiency

Question 46

Elective noncardiac surgery should be delayed ___ days after bare metal stent placement and ___ months after drug eluting stent placement

Answer 46

Elective noncardiac surgery should be delayed 30 days after bare metal stent placement and 6 months after drug eluting stent placement