Coagulation (Fluids ⅔) Flashcards by Grayson Young

Vascular Anatomy Graphic

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Coagulation Table Overview

Coagulation Overview Paragraph

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What are the 4 steps of hemostasis?

Vascular spasm
Primary hemostasis (formation of PLT plug)
Secondary hemostasis (coagulation & fibrin formation)
Fibrinolysis when the clot is no longer needed

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Platelets contain the following components EXCEPT:

Actin
Deoxyribonucleic acid
Adenosine diphosphate
Calcium

Deoxyribonucleic Acid (DNA)

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______________ produce platelets in the bone marrow.

Megakaryocytes

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What is the normal serum PLT value?

150,000 - 300,000 / mm³

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What is the lifespan of a platelet?

8 - 12 days (1 - 2 weeks)

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The ______ can sequester up to ⅓ of circulating platelets for later use.

spleen

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Platelets Overview

Platelets Components

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In the absence of vascular injury, the endothelium will inhibit platelet function by secreting what two things?

Prostaglandin I2 (inhibits vWF, TxA2)
Nitric Oxide (Inhibits TxA2 receptor)

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What external platelet receptors are there?

GPIb
ADP
TxA2
Thrombin
GPIIb-IIIa

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What clears platelets from the body?

Macrophages of the reticuloendothelial system and the spleen.

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What platelet hormone/transmitter helps activate nearby platelets?

serotonin

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What platelet component causes platelet activation & aggregation?

ADP

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What platelet component helps the platelet contract to form a platelet plug?

Actin

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What platelet outer structure (receptor) directly adheres to injured endothelium?

GP1b Receptors (Glycoprotein)

Adhere to expressed vWF from injured endolethium.

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What platelet component helps repair damaged vessel walls?

Growth Factor

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Which substance is responsible for adhering the platelet to the damaged vessel?

Thromboxane Α2
ADP
Tissue Factor
Von Willebrand Factor

Von Willebrand Factor

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Platelet adhesion to the damaged endothelium should be associated with ________________.

Von Willebrand Factor

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Platelet aggregation and activation should be associated with ____ and _____.

ADP and TXA2

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What is the immediate first thing to occur following vessel injury?

Vascular spasm

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What are the three steps of primary hemostasis (formation of platelet plug)?

Adhesion
Activation
Aggregation

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What is the process for platelet adhesion?

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What is the process for platelet activation?

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Which substance not only activates platelets but also vasoconstricts the vessel?

TXA2

An injured vessel will expose _________. What will be released when this occurs?

Collagen (is exposed) vWF and TF (tissue factor) are then released.

The ___________ receptor will link activated platelets together to form the platelet plug.

GPIIb-IIIa

What links platelets together?

GPIIb-IIIa & Fibrinogen

What is the process for platelet aggregation?

Though a platelet plug might be sufficient for a microinjury, what is needed to strengthen the platelet plug for more serious vascular injuries?

fibrin threads (and the rest of coag cascade)

The _____ pathway is activated when coagulation is initiated outside of the intravascular space.

extrinsic

The _______ pathway is activated when coagulation is initiated inside the intravascular space.

intrinsic

Classical Model Coagulation Paragraph

Cell-Based Coagulation Model Paragraph

How many coagulation factors are there?

12 *Factors 1 - 13, #6 doesn't exist!*

What is the mnemonic for the coagulation cascade factors? *This card is rough*

**Foolish People Try Climbing Long Slopes After Christmas, Some People Have Fallen** 1. Fibrinogen 2. Prothrombin 3. Tissue Factor 4. Calcium 5. Labile Factor 6. **doesn't exist** 7. Stable Factor 8. Antihemophilic Factor 9. Christmas Factor 10. Stuart-Prower Factor 11. Plasma Thromboplastin Antecedent 12. Hageman Factor 13. Fibrin Factor

Which two factors are **NOT** synthesized by the liver? Where do they come from?

3. Tissue factor = Vascular wall 4. Calcium = diet

Coagulation Cascade Pt. 1 *Learn to draw this*

Coagulation Cascade Pt. 2 *Learn to draw this*

Which factors are a part of the intrinsic (PTT) pathway?

8 9 11 12

Which factors are a part of the Extrinsic (PT) pathway?

3, 7

Which factor is a part of both the intrinsic and extrinsic pathways?

4 (Ca⁺⁺) is a cofactor in both pathways

Which factors are a part of the final common pathway?

1, 2 , 5, 10, 13

The intrinsic pathway is longer so its measured by _____.

PTT (more letters)

The extrinsic pathway is shorter so it's measured by _____.

PT (less letters)

Warfarin inhibits the _________ pathway.

**EX**trinsic

Which factors are vitamin k dependent?

2, 7, 9, 10 (circled numbers)

What is the **FIRST** coagulation factor activated in the extrinsic pathway? - Fibrinogen - Stuart-Prower Factor - Tissue Factor - Labile Factor

Tissue Factor

Detailed Extrinsic Pathway

Extrinsic Pathway Paragraph

What factor is the first to become deficient in patients with liver failure, vitamin k deficiency, and those on warfarin? Why?

Factor 7 (shortest half-life of all factors: 4 - 6 hours)

What factor is activated by TF?

Factor 7

What factor is activated by Factor 7? What else is required?

Factor 7 activates 10 in the presence of Ca⁺⁺ (factor 4)

How fast is the extrinsic pathway?

15 seconds!

Which factors are specific to the classical intrinsic pathway? **(Select 3)** - 4 - 6 - 7 - 8 - 9 - 11

- 8 - 9 - 11

What is another name for the intrinsic pathway?

Contact Activation Pathway

Detailed Intrinsic Pathway Pt.1

Detailed Intrinsic Pathway Pt.2

What is the first factor activated in the intrinsic pathway?

What is the order of factor activation for the intrinsic pathway?

12 → 11 → 9 → 10

What is the final step for both the intrinsic and extrinsic pathways?

Prothrombin activator & tissue phospholipids activate **Thrombin (factor 2a)**.

A deficiency in what factor causes Hemophilia A?

Factor 8

How long does it take to form a clot with the intrinsic pathway?

6 min

Injury activates the coagulation cascade by activating the extrinsic and/or intrinsic pathways. The primary goal of both pathways is to produce ______ _______.

prothrombin activator

The final common pathway begins when _____________ converts __________ to thrombin (2a).

prothrombinase (complex of 10a + 5a + 4) converts prothrombin (factor 2)

What does Thrombin (2a) do?

Changes fibrinogen to fibrinogen monomer ↓ With Ca⁺⁺ (4), fibrin fibers are created.

What occurs after fibrin fibers are created?

Final Common Pathway Paragraph

Final Common Pathway Graphic

Coagulation Cascade Graphic

What converts fibrinogen to fibrinogen monomer?

Thrombin

What must be present to convert fibrinogen monomer to fibrin fibers?

Ca⁺⁺ (Factor 4)

Identify the true statements regarding fibrinolysis. **(Select 2)** - D-dimer measures fibrin-split products - Plasminogen is synthesized in the endothelium - tPA inhibitor inhibits the conversion of fibrinogen to fibrin - Αlpha-2 antiplasmin inhibits the action of plasmin on fibrin

- D-dimer measures fibrin-split products - Αlpha-2 antiplasmin inhibits the action of plasmin on fibrin

What mechanisms limit the size of a clot forming?

What synthesizes plasminogen? Where does plasminogen "live" until its activated?

- Synthesized by liver - "Lives" in the clot dormant until activated

What enzyme degrades fibrin into fibrin degradation products?

Plasmin

What converts plasminogen to plasmin?

- tPa - Urokinase

Fibrinolysis Graphic

Plasmin Activation

What are the major and minor mechanism for plasminogen conversion to plasmin?

- tPa (major, released by injured tissue) - Urokinase (minor, produced by kidneys)

How is fibrinolysis "turned off" when no longer needed?

- PAI-1 (Plasminogen activator inhibitor 1) - Αlpha-2 antiplasmin

What are the 3 phases of the Cell-Based Model of the Coagulation Cascade?

1. Initiation 2. Amplification 3. Propagation

Initiation Phase (Cell-Based Coagulation)

Amplification Phase (Cell-based Coagulation)

Propagation Phase (Cell-based Coagulation)

What is the end result of the initiation phase of cell-based coagulation?

Small amount of Thrombin (2a) is produced (but not enough to activate fibrin)

In which phase are platelets activated in the contemporary coagulation model?

Amplification phase

Identify the **BEST** predictor of bleeding during surgery. - PT/INR - H&P - TEG - Bleeding time

H&P

What lab value will monitor the therapeutic response to unfractionated heparin but not LMWH?

aPTT

_________ (lab value) measure the intrinsic and final common pathways.

aPTT

What assesses the extrinsic and final common pathways?

Which lab test monitors the therapeutic response to warfarin?

PT (and INR)

What is a normal aPTT time?

25 - 32 seconds

What is a normal prothrombin time?

12 - 14 seconds

Which lab test measures the time it takes to form a clot using TF and Ca⁺⁺?

Which lab test measures the time it takes for form a clot using phospholipid, Ca⁺⁺, and an activator?

aPTT

What is a normal INR? What is a therapeutic INR on warfarin?

Normal: 1 Warfarin: 2 - 3

aPTT Paragraph

ACT Paragraph

PT Paragraph

INR Paragraph

What lab value guides heparin dosing?

ACT

What is normal ACT?

90 - 120 seconds

ACT should be greater than ______ before going on bypass.

400

What is a normal PLT count? What PLT increases surgical bleeding risk? What PLT increases spontaneous bleeding risk?

- Normal = 50,000 - 300,000 mm³ - Surgical bleeding < 50,000 mm³ - Spontaneous bledding < 20,000 mm³

What is a normal Bleeding time?

2 - 10 min

What is a normal D-dimer?

< 500 mg/mL

What does D-dimer monitor for?

Increased fibrinolysis thus → likely clot somewhere in body

What lab test measures the therapeutic response to Heparin?

aPTT *ACT will guide dosing*

What does the thromboelastogram in the image represent? - Primary fibrinolysis - Hypercoagulation - Factor 5 deficiency - DIC

Primary fibrinolysis

What are the two viscoelastic tests for monitoring "real-time" coagulation and fibrinolysis?

- TEG - ROTEM

TEG Graphic

TEG Table

What TEG states are seen in the picture below?

What TEG states are suggested by the shapes below?

Identify the part of the coagulation system that is assessed in each colored area.

Left to right: Coagulation factors → Fibrinogen → thrombin & fibrin → PLTs → Plasmin

Heparin inhibits the: - Extrinsic pathway - Intrinsic pathway - Extrinsic and final common pathways - Intrinsic and final common pathways

- Intrinsic and final common pathways

Where does endogenous heparin come from? Where does exogenous (pharmaceutical) heparin come from?

Endogenous = basophils, mast cells, and liver Exogenous = bovine lung & pig GI mucosa

What does Heparin bind to? What is the effect?

Antithrombin (ATIII), anticoagulant capability expands 1000x

The Heparin-ATIII complex neutralizes both ______ and factors ___, ___, ____, and ____.

Thrombin and factors 9, 10, 11, and 12

Failed heparinization should prompt consideration of ______ deficiency.

ATIII

Heparin MOA Paragraph

Heparin pharmacokinetics

How is heparin eliminated?

- Macrophage degradation - Renal excretion

What are the risks of heparin in pregnancy?

Normal bleeding risks - Heparin does NOT cross the placenta and is safe to give during pregnancy.

What is the cardiac surgery dose of heparin?

300 - 400 u/kg

What is the VTE prophylaxis dose of heparin?

5000u subcutaneous BID or TID

What is the active VTE dose of heparin?

5000u IV then 1250 u/hr

What is the therapeutic range of a heparinized aPTT?

1.5 - 2.5 times normal **40 - 80 seconds**

What is the unstable angina and acute MI dose of heparin?

5000u IV then 1000 u/hr

What factors will affect ACT time? (aside from heparin)

- Hypothermia - Thrombocytopenia - deficiency of fibrinogen, factor 7, and/or factor 12

Heparin Side Effects

Heparin Contraindications

What system clears a heparin-protamine complex?

Reticuloendothelial system (mononuclear macrophage system)

Protamine Reversal Paragraph

Protamine Reactions

Warfarin inhibits factors: - 3 and 10 - 2, 7, 9, and 10 - 2, 7, 9, 10, and protein C - 2, 7, 9, 10, and protein C and protein S

- 2, 7, 9, 10, and protein C and protein S

What drug inhibits the enzyme vitamin K reductase complex 1 (VKOR c1)?

Warfarin *prevents inactive vitamin k from becoming active*.

Why does warfarin take 36 - 72 hours to achieve therapeutic concentration?

What is the "antidote" for warfarin?

- Vitamin K - FFP - 4-factor PCC's

Warfarin Paragraph

Vitamin K Paragraph

What are risk factors for vitamin K deficiency?

__________ is another name for pharmaceutical IV administered vitamin K.

Phytonadione

Vitamin K supplementation requires which organ to be healthy?

Liver

What is the dose of Vitamin K?

10 - 20 mg PO, IM, or IV

IV administration of Vitamin K is associated with what life-threatening side effect?

Anaphylaxis → give at 1mg/min to limit this

Vitamin K Anesthetic Implications

Where are the body's two sources of inactive Vitamin K?

- Diet - Gut bacteria

Antiplatelet Drugs

Anticoagulants & Fibrinolytics

Are NSAIDs or Aspirin's effects on COX-1 reversible?

NSAIDs = reversible Aspirin = irreversible

Drugs that Treat Bleeding

Fibrinolytcs vs Antifibrinolytics

How does TXA work?

Prevents conversion of plasminogen to plasmin

What antibleeding agent stimulates the release of factor 8 and vWF?

DDAVP

Von Willebrand Disease Paragraph

What are the three classifications of Von Willebrand Disease?

What synthesizes Von Willebrand Factor ?

- Vascular endothelium - Megakaryocytes

What are the two key functions of Von Willebrand Factor?

1. Platelet adhesion to vessel wall 2. Carries inactivated factor 8 in the plasma

What two lab tests are elevated with Von Willebrand Disease?

- PTT - Bleeding Time

What drug stimulates the release of vWF and increases Factor 8 activity?

Desmopressin

Patients with what vWF Disease type respond best to desmopressin? Which do not?

Von Willebrand Disease Type 1 *Type 3 do NOT respond to desmopressin*

What is the dose of desmopressin?

0.3 mcg/kg IV

Desmopressin Paragraph

Blood Products Paragraph

What is contained in cryoprecipitate?

Factors 8 & 13 Fibrinogen (Factor 1) vWF

What is the first-line agent for patients suffering from Type 3 Von Willebrand Disease?

Purified 8-vWF concentrate

Which coagulopathies present with a prolonged PTT and a **normal** PT? **(Select 2)** - Hemophilia A - Hemophilia B - Factor 10 deficiency - Factor 2 deficiency

- Hemophilia A - Hemophilia B

Hemophilia A is associated with Factor ___ deficiency.

How will lab values be affected with Hemophilia A?

- ↑ PT - All else normal

What should a Hemophilia A patient receive prior to surgery?

- Factor 8 Concentrate - FFP & Cryo (less optimal)

Hemophilia B is associated with Factor __ deficiency.

What are the anesthetic implications of Hemophilia B?

Hemophilia & Factor 7 Paragraph

Which type of hemophilia is considered more severe?

Hemophilia A

Which pathway of the coagulation cascade is affected by Hemophilia A & B?

Intrinsic (thus ↑PTT)

Options: - Heparin infusion - TXA - FFP - Albumin

- FFP

DIC Overview

What lab changes are seen with DIC?

- ↑ PT/PTT - ↑ D-dimer - ↓ PLTs - ↓ Fibrinogen

DIC Short Summary

DIC Detailed Summary

What are signs of DIC?

What patients are at risk of developing DIC the most?

- Sepsis - Pregnant - Malignancy

What is the treatment for DIC?

A patient with a history of type 2 heparin-induced thrombocytopenia requires anticoagulation for cardiopulmonary bypass. What is the **BEST** treatment? - Enoxaparin - Heparin test dose - Warfarin - Bivalirudin

Bivalirudin

Patients with antithrombin deficiency are unresponsive to ______.

heparin

ATIII Deficiency Summary

What is the treatment for ATIII deficiency?

- Antithrombin concentrate - FFP

What is the pathophysiology of HIT?

Differentiate HIT type 1 and HIT type 2.

Which type of Heparin-Induced Thrombocytopenia is the more severe type?

HIT Type 2

What are protein C and S deficiency?

Factor 5 Leiden mutation causes a resistance to the anticoagulant effects of ________ __.

Protein C

What is the treatment for Protein C and S deficiency?

What is the treatment for Factor 5 Leiden Mutation?

- None unless patient experiences recurrent thrombotic events

What 4 factors are inactivated by Antithrombin?

12, 11, 9, and 10

Protein C inhibits which factors?

5a and 8a

What is the role of protein S?

It is a cofactor that helps Protein C

Triggers of sickle cell crisis include: **(Select 2)** - Alkalosis - Hyperthermia - Pain - Dehydration

- Pain - Dehydration

What is the pathophysiology of sickle cell anemia?

What are the triggers that must be avoided to prevent sickle cell crisis?

- Pain - Hypothermia - Hypoxemia - Acidosis - Dehydration

What is the most common manifestation of sickle-cell disease?

Vaso-Occlusive Crisis

What is the most significant source of mortality surrounding sickle cell disease?

Acute Chest Syndrome

Sickle Cell Complications Pt.1

Sickle Cell Complications Pt.2

What is Sickle Cell Trait?

What condition can progress a patient with sickle cell trait into full crisis?

Severe hypoxemia

Select the **BEST** treatment for a prolonged R time on the TEG. - Cryo - Desmopressin - FFP - TXA

FFP

A deficiency in which mediators favor hypercoagulability? - Αlpha-Antiplasmin - Antithrombin - Protein S - Fibronectin

- Antithrombin - Protein S

Severe liver failure will reduce the synthesis of which coagulation factors? **(Select 2)** - 1 - 3 - 8 - 4

- 1 - 8

Patients who are deficient in Protein C are at risk for: - Thrombosis - Spontaneous Hemorrhage - Vaso-occlusive disease - Acute chest syndrome

Thrombosis

Which clotting factor has the shortest half-life? - 9 - 10 - 7 - 2

- 7

Which condition places a patient at the **GREATEST** risk of developing DIC? - Gram-negative sepsis - Adenocarcinoma - Preeclampsia - Placental abruption

Gram-negative Sepsis

Which laboratory test measures the extent of fibrin breakdown? - Antithrombin assay - D-dimer - Bleeding time - Thrombin time

- D-dimer

Rapid administration of desmopressin will **MOST** likely cause: - Bronchospasm - Thrombosis - Hyperglycemia - Hypotension

Hypotension

Which anesthetic modalities reduce the incidence of morbidity in patients with sickle cell disease? **(Select 2)** - Forced-air warmer - Hydromorphone - Permissive hypercapnia - Fluid restriction

- Forced-air warmer - Hydromorphone

Coagulation (Fluids ⅔) Flashcards

(200 cards)