27 Hemostasis and Coagulation Flashcards

1
Q

Describe the components of normal hemostasis and laboratory evaluation

Hemostasis:
- Bleeding is controlled through clotting: ?
- Clot breakdown = ?

A

Hemostasis:
- Bleeding is controlled through clot formation (thrombus)
- Eventual clot breakdown (fibrinolysis)

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2
Q

Describe the components of normal hemostasis and laboratory evaluation

Primary Hemostasis:
- Injury to blood vessel exposes ?
- Two things happen to stop flow:
1. ?
2. ?

A

Primary Hemostasis:
- Injury to blood vessel exposes collagen below endothelium
- Two things happen to stop flow:
1. Vasoconstriction
2. Platelet Plug formation

Primary hemostasis is a procoagulation clot forming process associated with the initiation and formation of the platelet plug

Primary hemostasis is a procoagulation clot forming process associated w

Platelets:
- 3-4um cell fragments
- Thrombocytes
- Primary hemostasis: Adhesion // Aggregation
- Role in 2° hemostasis

Secondary hemostasis also a procoagulation clot forming process and it is associated with the propagation of the clotting process via the intrinsic and extrinsic coagulation cascades.

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3
Q

Describe the components of normal hemostasis and laboratory evaluation

Platelets:
- what are they? ?
- aka ?
- Encourage primary hemostasis via three major processes: ? // ? // ?
- Role in 2° hemostasis
- activated platelets provide an efficient ? for the assembly of the ? of the blood coagulation system, also known as secondary hemostasis.

A

Platelets:
- what are they? 3-4um cell fragments
- aka Thrombocytes
- Encourage primary hemostasis via three major processes: Activation // Adhesion // Aggregation
- Role in 2° hemostasis
- activated platelets provide an efficient catalytic surface for the assembly of the enzyme complexes of the blood coagulation system, also known as secondary hemostasis.

Platelets, or thrombocytes, are small, colorless cell fragments in our blood that form clots and stop or prevent bleeding.
- made in our bone marrow (contains stem cells that develop into red blood cells, white blood cells, and platelets)
- component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby initiating a blood clot.

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4
Q

Describe the components of normal hemostasis and laboratory evaluation

Platelet Adhesion:
- ? on platelet binds to ? (soluble glycoprotein) which binds to exposed ?

Activated platelets change ?, express ?, and release ?

A

Adhesion:
- Glycoprotein Ib/IX on platelet binds to von Willebrand Factor (soluble glycoprotein) which binds to exposed collagen

Activated platelets change shape, express fibrinogen receptors, and release granules

Aggregation
Glycoprotein IIb/IIIa
binds
Fibrinogen (soluble protein) binds Glycoprotein IIb/IIIa

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5
Q

Describe the components of normal hemostasis and laboratory evaluation

Platelet Aggregation:
Glycoprotein ?
binds
? (soluble protein)
binds
?

A

Platelet Aggregation:
Glycoprotein IIb/IIIa
binds
Fibrinogen (soluble protein)
binds
Glycoprotein IIb/IIIa

Activated glycoprotein IIb/IIIa receptors become receptive to fibrinogen, and when fibrinogen binds to the glycoprotein IIb/IIIa receptors located on two different platelets it builds the cross-links for platelet-to-platelet aggregation. The glycoprotein IIb/IIIa also mediates platelet adhesion and spreading.

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6
Q

Describe the components of normal hemostasis and laboratory evaluation

What glycoprotein is responsible for platelet aggregation?

A

Activated glycoprotein IIb/IIIa receptors become receptive to fibrinogen, and when fibrinogen binds to the glycoprotein IIb/IIIa receptors located on two different platelets it builds the cross-links for platelet-to-platelet aggregation.
The glycoprotein IIb/IIIa also mediates platelet adhesion and spreading.

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7
Q

Describe the components of normal hemostasis and laboratory evaluation

Lab Evaluation of Primary Hemostasis:
- ? count
- ?
- ? studies
- ? level and function
- ? level

A

Lab Evaluation of Primary Hemostasis:
- Platelet count (140-400x10^9/L)
- Morphology
- Platelet Aggregation studies
- Von Willebrand Factor level and function
- Fibrinogen level

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8
Q

Describe the components of normal hemostasis and laboratory evaluation

Secondary Hemostasis:
- Triggered by ?
- Results in ?
- Aids in ?
- Three pathways: ?

A

Secondary Hemostasis:
- Triggered by Tissue Factor (TF) from epithelial cells at the site of injury
- Results in conversion of Fibrinogen to Fibrin -> Fibrin Clot Formation
- Aids in Clot stabilization
- Three pathways:
1. Intrinsic
2. Extrinsic
3. Common

Secondary hemostasis refers to the cascade of enzymatic reactions that ultimately results in the conversion of fibrinogen to fibrin monomers

Secondary hemostasis is triggered by the release of tissue factor from epithelial cells that are exposed to the circulation at the site of vascular injury. Defects in secondary hemostasis decrease fibrin production and reduce the stability of the formed clot.

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9
Q

Describe the components of normal hemostasis and laboratory evaluation

Secondary Hemostasis: Intrinsic Pathway
- Factors involved:
- ? is activated by collagen
- ? needs other mediators (HMWK, Prekallikrein) to be activated
- ? is a source of phospholipid
- Ca2+-PF3-FVII = ? complex - to activate FX in the common pathway

A

Secondary Hemostasis: Intrinsic Pathway
- Factors involved: XII // XI // IX // VIII (12, 11, 9, 8)
- FXII is activated by collagen
- FXI needs other mediators (HMWK, Prekallikrein) to be activated
- PF3 = Platelet Factor 3 is a source of phospholipid
- Ca2+-PF3-FVII = Tenase complex - to activate FX in the common pathway

This pathway is the longer pathway of secondary hemostasis. It begins with the activation of Factor XII (a zymogen, inactivated serine protease) which becomes Factor XIIA (activated serine protease) after exposure to endothelial collagen

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10
Q

Describe the components of normal hemostasis and laboratory evaluation

Secondary Hemostasis: Extrinsic Pathway
- Factors involved: 2
- ? is released from injured vessel wall
- ? and ? forms a complex to activate FX in the common pathway
- ? complex can activate FIX in the intrinsic pathway

A

Secondary Hemostasis: Extrinsic Pathway
- Factors involved: TF // FVII
- Tissue Factor (TF) is released from injured vessel wall
- FVIIa and TF forms a complex to activate FX in the common pathway
- FVIIa:TF can activate FIX in the intrinsic pathway

The extrinsic pathway is the shorter pathway of secondary hemostasis.
Once the damage to the vessel is done, the endothelial cells release tissue factor which goes on to activate factor VII to factor VIIa.
Factor VIIa goes on to activate factor X into factor Xa

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11
Q

Describe the components of normal hemostasis and laboratory evaluation

Secondary Hemostasis: Common Pathway
- Factors involved: 4
- ? is activated from both pathways
- ? ? and ? helps with thrombin production
- ? is produced
- ? forms a stable Clot

A

Secondary Hemostasis: Extrinsic Pathway
- Factors involved: X, V, II, I
- FX is activated from both pathways
- FV Ca+2 and PF3 helps with thrombin production
- Fibrin is produced
- FXIII forms a stable Clot

PF3 = platelet factor 3

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12
Q

Coagulation Cascade

Describe the coagulation cascade in vitro
How does in-vivo differ?

A

Intrinsic: Collagen activates FXII to FXIIa: 12→11→9→8→10 (common)

Extrinsic: 3 + TF + Ca →7→9 (intrinsic) // 10 (common)

Common: X + FV (5) + Ca → Prothrombin (FII) + Ca + PF3 + FV (5) → Thrombin (FIIa) →Fibrinogen → Fibrin

In vivo, Thrombin (FIIa) activates Factors 5, 7, 8, 11, 13

PF3 = Platelet factor 3

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13
Q

Describe the components of normal hemostasis and laboratory evaluation

Lab Evaluation of Secondary Hemostasis:
- PTT =?
- PT-INR = ?
- ?
- Patient plasma used to measure ? to ?

A

Lab Evaluation of Secondary Hemostasis:
- PTT =Activated Partial Thromboplastin Time
- PT-INR = Prothrombin Time
- Fibrinogen
- Patient plasma used to measure time (seconds) to clot

If one or more factors are reduced, clotting time is prolonged
Fibrinogen is helpful
PT time (seconds) converted to ratio (INR) for standardization

PTT measures intrinsic (Factors 12,11,9,8) and Common (Factors X, V, II, I) Pathway

PT measures extrinsic (VII) and common (X, V, II, I) pathways

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14
Q

Discuss acquired bleeding disorders and give examples

  • Alcohol:
  • Liver and Kidney failure
  • Cardiopulmonary Bypass
  • Some marrow failure syndromes and hematologic disorders
  • Acidosis, Hypothermia, Hypocalcemia
  • Disseminated Intravascular Coagulopathy (DIC)
A

Alcohol: interferes with the clotting process in a couple of ways:
- reduces number of platelets in the blood, in part by interfering with blood cell production in the bone marrow.
- It makes the platelets you do have less sticky.

Platelet disorders are the most common cause of bleeding disorder and are usually acquired rather than inherited.

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15
Q

Discuss acquired bleeding disorders and give examples

  • Alcohol
  • Liver and Kidney failure
  • Cardiopulmonary Bypass
  • Some marrow failure syndromes and hematologic disorders
  • Acidosis, Hypothermia, Hypocalcemia
  • Disseminated Intravascular Coagulopathy (DIC)
A

The liver plays a central role in the clotting process, and acute and chronic liver diseases are invariably associated with coagulation disorders due to multiple causes:
- decreased synthesis of clotting and inhibitor factors,
- decreased clearance of activated factors,
- quantitative and qualitative platelet defects,
- hyperfibrinolysis, and
- accelerated intravascular coagulation

Platelet dysfunction is the main factor responsible for hemorrhagic tendencies in advanced kidney disease. Anemia, dialysis, the accumulation of medications due to poor clearance, and anticoagulation used during dialysis have some role in causing impaired hemostasis in ESRD patients

Platelet disorders are the most common cause of bleeding disorder and are usually acquired rather than inherited.

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16
Q

Discuss acquired bleeding disorders and give examples

  • Alcohol
  • Liver and Kidney failure
  • Cardiopulmonary Bypass
  • Some marrow failure syndromes and hematologic disorders
  • Acidosis, Hypothermia, Hypocalcemia
  • Disseminated Intravascular Coagulopathy (DIC)
A

CPB is a traumatic procedure that is associated with platelet and coagulation defects, inflammation, and increased fibrinolysis

Platelet disorders are the most common cause of bleeding disorder and are usually acquired rather than inherited.

17
Q

Discuss acquired bleeding disorders and give examples

  • Alcohol
  • Liver and Kidney failure
  • Cardiopulmonary Bypass
  • Some marrow failure syndromes and hematologic disorders
  • Acidosis, Hypothermia, Hypocalcemia
  • Disseminated Intravascular Coagulopathy (DIC)
A

Bone marrow failure syndromes are rare diseases characterized by an inability to make enough blood – either red cells, which carry oxygen; white cells, which fight infection; or platelets, which help the blood clot. Bone marrow failure disorders may be either inherited or acquired.

Platelet disorders are the most common cause of bleeding disorder and are usually acquired rather than inherited.

18
Q

Discuss acquired bleeding disorders and give examples

  • Alcohol
  • Liver and Kidney failure
  • Cardiopulmonary Bypass
  • Some marrow failure syndromes and hematologic disorders
  • Acidosis, Hypothermia, Hypocalcemia
  • Disseminated Intravascular Coagulopathy (DIC)
A

Acidosis compromised the clotting process and accelerated fibrinogen consumption with no effect on fibrinogen production, resulting in a deficit in fibrinogen availability.

Hypothermia has been shown to result in hemoconcentration, leukopenia and thrombocytopenia, slowing down of coagulation enzymes, disordered fibrinolysis, and disruption of platelet function

Hypocalcemia: A high deficiency can also form blood clots which reduce blood flow. When you sustain a minor injury, blood will form easily, and the blood clot forms slowly. This risks the chance of more blood flow release. Calcium has a strong link to blood clotting

Platelet disorders are the most common cause of bleeding disorder and are usually acquired rather than inherited.

19
Q

Discuss acquired bleeding disorders and give examples

  • Alcohol
  • Liver and Kidney failure
  • Cardiopulmonary Bypass
  • Some marrow failure syndromes and hematologic disorders
  • Acidosis, Hypothermia, Hypocalcemia
  • Disseminated Intravascular Coagulopathy (DIC)

DIC:
- What is it?

In stage one,
- ? leads to blood clots throughout the blood vessels - can ?, which can damage organs.

In stage two, as DIC progresses,
- the overactive clotting uses up ? and ? that help the blood to clot.
- Without these, DIC leads to ?

Caused by:
- ?
- ?
- ?

Lab indicators:
- ?,
- low ?,
- ?

A

DIC:
- Widespread clotting throughout the body rather than site of injury (life threatening)

In stage one,
- overactive clotting leads to blood clots throughout the blood vessels - can reduce or block blood flow, which can damage organs.

In stage two, as DIC progresses,
- the overactive clotting uses up platelets and clotting factors that help the blood to clot.
- Without these platelets and clotting factors, DIC leads to bleeding just beneath the skin, in the nose or mouth, or deep inside the body.

Causes:
- Sepsis
- Trauma
- Underlying conditions - pancreatitis, cancer, blood transfusion reactions

Lab indicators:
Prolonged PT, PTT, low fibrinogen, platelets as factors and platelets are consumed

PT = Prothrombin Time = A prolonged PT means that the blood is taking too long to form a clot.

PTT = Partial Thromboplastin Time = show how much time it took for your blood to clot. Results are usually given as a number of seconds. If your results show that your blood took a longer-than-normal time to clot, it may mean you have: A bleeding disorder, such as hemophilia or von Willebrand disease

20
Q

Describe the pathophysiology, laboratory diagnosis and treatment of Hemophilia A, and von Willebrand Disease.

Hemophilia A
- ? bleeding disorder caused by a lack of blood clotting factor ?
- Factor ? deficiency = ~1/5500
- Factor ? deficiency = ~1/20000

Presentation
- Mild - ?
- Moderate - ?
- Severe - ?

Treatment:
- ?
- ? (human source blood products

A

Hemophilia A
- hereditary bleeding disorder caused by a lack of blood clotting factor VIII. Without enough factor VIII, the blood cannot clot properly to control bleeding
- Factor VIII deficiency = ~1/5500
- Factor IX deficiency = ~1/20000

Presentation
- Mild - bleeding with trauma
- Moderate - Bleeding with minor injury
- Severe - Spontaneous bleeding

Treatment:
- Recombinant FVIII or FIX
- Factor Concentrates (human source blood products

21
Q

Describe the pathophysiology, laboratory diagnosis and treatment of Hemophilia A, and von Willebrand Disease.

Von Willebrand Disease:
- Acquisition?? ? ~ 1/100
- Decreased vWF affects ?
- Severity ?

Treatment:
- Drugs (?) to increase ?
- ? (Blood product)

A

Von Willebrand Disease:
- Autosomal Dominant ~ 1/100
- Decreased vWF affects primary hemostasis
- Bruising, nosebleeds, bleeding gums, excessive bleeding during surgery
- Mild to moderate

Treatment:
- Drugs (desmopressin) to increase vWF:FVIII
- vWF concentrate (Blood product)

22
Q

Describe the mechanism of action of common anticoagulant drugs.

  • Treat/Prevent ?
  • ? Tx for those at risk (risk factors: ?)
  • Inhibit ?
  • May require ?
A

Describe the mechanism of action of common anticoagulant drugs.

  • Treat/Prevent thrombosis
  • Prophylactic Tx for those at risk (risk factors: Myocardial infarction // Pulmonary Embolism // Stroke // Deep vein thrombosis)
  • Inhibit one or more components of hemostasis
  • May require lab monitoring

Thrombosis occurs when blood clots block your blood vessels. There are 2 main types of thrombosis: Venous thrombosis is when the blood clot blocks a vein. Veins carry blood from the body back into the heart. Arterial thrombosis is when the blood clot blocks an artery

23
Q

Describe the mechanism of action of common anticoagulant drugs.

Platelets:
- ?, ? - Inhibit platelet function aggregation

Factor Inhibitors:
? - Inhibit factors II, VII, IX, X (Vitamin K dependent factors)
- Monitor ?

? - Amplifies inhibitor ATIII which inhibits FII, FXa, FVIII, FV, platelets
- Monitor ?

A

Platelets:
- ASA, Clopidogrel - Inhibit platelet function aggregation

Factor Inhibitors:
Warfarin - Inhibit factors II, VII, IX, X (Vitamin K dependent factors)
- Monitor PT-INR PT = Prothrombin time

Heparin - Amplifies inhibitor ATIII which inhibits FII, FXa, FVIII, FV, platelets
- Monitor PTT (Partial thromboplastin time)

Anticoagulants - Treat/Prevent thrombosis
- Prophylactic Tx for those at risk (risk factors: Myocardial infarction // Pulmonary Embolism // Stroke // Deep vein thrombosis)
- Inhibit one or more components of hemostasis
- May require lab monitoring

PTT is a blood test used to measure a patient’s response to treatment with unfractionated heparin infusion. While PTT does not measure anticoagulation directly, it measures the effect on blood clotting

For people taking warfarin, most laboratories report PT results that have been adjusted to the INR. These people should have an INR of 2.0 to 3.0 for basic “blood-thinning” needs. For some who have a high risk of a blood clot, the INR needs to be higher – about 2.5 to 3.5

24
Q

Describe the mechanism of action of common anticoagulant drugs.

Platelets:
- ASA, Clopidogrel - Inhibit ?

Factor Inhibitors:
Warfarin:
- Inhibit factors 4 (? dependent factors)
- Monitor ?

Heparin:
- Amplifies ? which inhibits ?, ?, ?, ?, ?
- Monitor ?

A

Platelets:
- ASA, Clopidogrel - Inhibit platelet function aggregation

Factor Inhibitors:
Warfarin
- Inhibit factors II, VII, IX, X (Vitamin K dependent factors)
- Monitor PT-INR (PT = Prothrombin time)

Heparin
- Amplifies inhibitor ATIII (antithrombin) which inhibits FII, FXa, FVIII, FV, platelets
- Monitor PTT (Partial thromboplastin time)

Anticoagulants - Treat/Prevent thrombosis
- Prophylactic Tx for those at risk (risk factors: Myocardial infarction // Pulmonary Embolism // Stroke // Deep vein thrombosis)
- Inhibit one or more components of hemostasis
- May require lab monitoring

PTT is a blood test used to measure a patient’s response to treatment with unfractionated heparin infusion. While PTT does not measure anticoagulation directly, it measures the effect on blood clotting

For people taking warfarin, most laboratories report PT results that have been adjusted to the INR. These people should have an INR of 2.0 to 3.0 for basic “blood-thinning” needs. For some who have a high risk of a blood clot, the INR needs to be higher – about 2.5 to 3.5