Blood and Coagulation Flashcards
1
Q
What is the formula for the Maximal Allowable Blood Loss (MABL)
A
EBV x (initial Hct - lowest acceptable Hct) / Initial Hct
2
Q
What is the estimated blood volume (EBV) for obese patients?
A
60mL/kg
3
Q
What is the estimated blood volume (EBV) for adult male patients?
A
70mL/kg
4
Q
What is the estimated blood volume (EBV) for adult female patients?
A
65mL/kg
5
Q
What is the estimated blood volume (EBV) for preemie patients?
A
95-105mL/kg (more blood volume per kg body weight)
6
Q
What is the estimated blood volume (EBV) for term infant patients?
A
85mL/kg
7
Q
What is the estimated blood volume (EBV) for infants under one year?
A
80mL/kg
8
Q
What is the estimated blood volume (EBV) for children ages 1-6 years old?
A
70-75 mL/kg
9
Q
What is the lowest acceptable Hct based on?
A
Based on the patient’s comorbidities. The general number is 20-21%.
10
Q
Which substance is responsible for adhering the platelet to the damaged vessel?
A
von Willebrand Factor
11
Q
Which substances are associated with platelet activation and aggregation with?
A
The endothelium releases collagen which activates platelets to release ADP and Thromboxane A2.
12
Q
The 4 steps of Hemostasis
A
- Vascular Spasm
- Formation of the platelet Plug (primary hemostasis)
- Coagulation and Fibrin formation (secondary hemostasis)
- Fibrinolysis when the clot is no longer needed
13
Q
What and Where are platelets produced?
A
Megakaryocytes produce platelets in the bone marrow
14
Q
What is the lifespan of platelets?
A
8-12 days (1-2 weeks)
15
Q
What removes platelets?
A
Cleared by macrophages
16
Q
Normal lab value for platelets?
A
150,000-300,000
(some texts say 100,000)
17
Q
In the absence of vascular injury, the endothelium inhibits platelet function by :
A
Prostaglandin I2, NO, and ADP: inhibit platelet aggregation
Thrombomodulin: Binds thrombin and interferes with Protein C activation. This stops the inactivation of factors 5 and 8, which promotes thrombosis.
Releases t-PA: activates fibrinolysis
18
Q
What is the function of Actin in platelets?
A
Helps the platelet contract to form a platelet plug
19
Q
What is the function of the GpIIb/IIIa receptor complex compared to the GpIb receptors?
A
The GpIIb/IIIa receptor complex links activated platelets together to form a primary platelet plug on the platelet surface.
The GpIb emerges from the surge of the platelet to attach vWF and attract platelets to the endothelial lining.
20
Q
What are the 2 functions of Vascular Spasm?
A
- reduces blood flow to area to minimize blood loss
- Helps procoagulants remain in the affected area so that they can do their job
21
Q
During vasular injury, platelets adhere to collagen via?
A
Glycoprotein Ib of platelets to VWF. vWF functions as an adhesion bridge between subendothelial collagen and the GpIb receptor on platelets.
22
Q
How does Von Willebrand factor (vWF) adhere to platelets?
A
vWF is synthesized and released from the endothelium. Binds the Glycoprotein 1b receptor on platelets and anchors them to the subendothelium
23
Q
Activated platelets release? These substances do what?
A
Release ADP and Thromboxane A2. They recruit nearby platelets and facilitate platelet aggregation
24
Q
Activated platelets release the contents of their alpha granules, this includes:
A
Fibrinogen, Fibronectin, vWF, platelet factor 4, platelet growth factor
25
Activated platelets express two glycoproteins on their surface, they are?
Gp IIb and Gp IIIa
26
What are the 3 steps of Primary Hemostasis (Platelet Plug Formation)
1. Adhesion
2. Activation
3. Aggregation
27
What receptor complex links activated platelets together to form the platelet plug
Gp IIb/IIIa
28
What is required for Gp IIb/IIIa to accept fibrinogen?
Thromboxane A2 and ADP configure the receptor complex to accept fibrinogen
29
Do micro-injuries require a clot or only a platelet plug
Only a platelet plug. The more significant vascular injury requires a clot
30
The primary purpose of the coagulation cascade is to produce?
Fibrin (to form a clot)
31
Two distinct coagulation pathways arrive at the same endpoint to form the final common pathway. What point in the cascade is this?
Thrombin Activation - 2a
32
The extrinsic pathway is activated when?
Coagulation is initiated outside the intravascular space
33
The intrinsic pathway is activated when?
Coagulation is initiated inside the intravascular space
34
What coagulation factors are Vitamin K dependent?
Factors 2, 7, 9, 10
35
Factor 1 is _____ and is synthesized in the _____. Its function is?
Fibrinogen and Liver
Clot formation
36
Factor 2 is _____ and synthesized in the _____. Its function is?
Prothrombin and Liver
When in active form (Thrombin), it activates Factors 1, 5, 8, 11,13, platelets, and Protein C
37
Factor 3 is _____ and synthesized in the _____. Its function is?
Tissue Factor
Vascular Wall + Extravascular Cell Membranes; released from traumatized cells
Cofactor for Factor 7
38
Factor 4 is _____ and synthesized in the _____. Its function is?
Calcium Ions and Diet
Promotes clotting reactions
39
Factor 5 is _____ and synthesized in the _____. Its function is?
Proaccelerin (Labile Factor) and Liver
Cofactor for Factor 10. Forms prothrombinase complex
40
Factor 7 is _____ and synthesized in the _____. Its function is?
Proconvertin (Stable Factor) and Liver
Activates Factor 9 and 10
41
Factor 8 is _____ and synthesized in the _____. Its function is?
Antihemophilic Factor and Liver
Cofactor to Factor 9
42
Factor 9 is _____ and synthesized in the _____. Its function is?
Christmas Factor and Liver
Activates Factor 10
43
Factor 10 is _____ and synthesized in the _____. Its function is?
Stuart-Prower Factor and Liver
Activates Factor 2, forms prothrombinase complex with Factor 5
44
Factor 11 is _____ and synthesized in the _____. Its function is?
Plasma Thromboplastin Antecedent and Liver
Activates Factor 9
45
Factor 12 is _____ and synthesized in the _____. Its function is?
Hageman Factor and Liver
Activates Factor 11
46
Factor 13 is _____ and synthesized in the _____. Its function is?
Fibrin Stabilizing Factor and Liver
Cross Links Fibrin
47
What two factors are not blood proteins?
Factor 3 - Tissue Factor
Factor 4 - Calcium Ions
48
The Intrinsic Pathway is measured by?
PTT (more letters - intrinsic longer than extrinsic)
49
The Extrinsic Pathway is measured by?
PT (less letters - shorter than intrinsic)
50
The extrinsic pathway is activated by?
Tissue Factor - factor 3
51
Which coagulation factor has the shortest half-life? What is the implication of this?
Factor 7 - shortest half-life of about 4-6hrs.
It will be the first factor to become deficient in patients with liver failure, Vitamin K deficiency, and those on warfarin
52
How fast is the extrinsic pathway?
Fast - requires only about 15 seconds
53
What factors are specific to the extrinsic pathway
Factor 7 (Stable Factor)
Factor 3 (Tissue Factor)
54
What factors are specific to the intrinsic pathway
12 (Hageman Factor)
11 (Plasma Thromboplastic Antecendent)
9 (Christmas Factor)
8 (Antihemophilic Factor)
55
How long does it take the intrinsic pathway to form a clot?
Up to 6 minutes
56
A deficiency of what factor causes Hemophilia A?
Factor 8 (Antihemophilic Factor)
57
What is the role of thrombin
Converts fibrinogen to fibrinogen monomer
Activates or is a cofactor for 1, 13, 5, 8, 11
58
What must be present to convert fibrinogen monomer to fibrin fibers?
Calcium (factor 4)
59
Once a clot is degraded, how does the body turn off the fibrinolytic process?
tPA inhibitor (TPAI) inhibits the conversation of plasminogen to plasmin
Alpha-2 antiplasmin inhibits the action of plasmin on fibrin
60
What is plasmin?
A proteolytic enzyme that degrades fibrin into fibrin degradation products.
61
How is Plasmin activated?
Injured tissue releases tissue plasminogen activator (tPA) over a period of days (major mechanism)
Urokinase is produced by the kidneys and releases into the circulation (minor mechanism)
62
What are 4 mechanisms that counterbalance clot formation?
1. Vasodilation and washout of ADP and TxA2
2. Antithrombin inactivating thrombin
3. Tissue factor pathway inhibitor neutralizes tissue factor
4. Release of proteins C and S
63
What are 2 enzymes that convert plasminogen to plasmin
tPA and urokinase
64
What 2 enzyme inhibitors turn off the fibrinolytic process?
tPA inhibitor (TPAI)
Alpha-2 antiplasmin
65
How are plasmin activators used therapeutically?
They help dissolve thrombi to restore blood flow
66
The contemporary cell-based cascade consists of three phases. They are?
1. Initiation
2. Amplification
3. Propagation
67
What is the end result of the initiation phase within the contemporary cell-based cascade?
A small amount of Thrombin (2a) is produced but not enough to activate fibrin.
68
Why do thrombin levels remain low in the first phase of the contemporary coagulation model?
Because tissue factor pathway inhibitor (TFPI) limits the amount of tissue factor released
69
What phase are platelets activated in the contemporary coagulation model?
Amplification
70
Chapter 10 Apex Left Off
71
How does Tissue Factor (3) not continually activate the extrinsic pathway?
When Tissue Factor activates Factor 7, it is immediately inhibited by TF Inhibitor so only a predetermined amount of factor becomes activated.
72
Going from Extrinsic Pathway to Common, after Factor 7 is activated, it then activates?
Activates Factor 10 (X) of the common pathway
73
What 3 factors are needed to activate Thrombin from Prothrombin?
Factor 10a, 5a, and Factor 4
(Stuart Power, Proaccelerin, and Calcium)
74
What 2 factors form the Prothrombinase Complex?
Factor 10a and 5a
75
Thrombin (2a) + Calcium (4) =?
Convertes Fibrinogen to Fibrin
76
The Intrinsic Pathway (Contact Activation Pathway) is initiated when?
Damage occurs to the blood vessels themselves.
77
The Extrinisic Pathway (TF Pathway) becomes activated when?
By the release of TF when injury occurs outside the vessel wall (organ trauma or crushing injuries)
78
What is the first factor to become activated in the Intrinsic Pathway?
Factor 12 (Hageman)
79
Thrombin ASSISTS with the activation of which Factors?
5, 8, 1, 11 and 13
And influences the recruitment of platelets to the injured area
80
How does Thrombin act as an anticoagulant?
1. Prevents continuous clot formation by releasing Tissue Plasminogen Factor (tPA)
2. Stimulates Protein C and S to inhibit clot formation
3. Forms a relationship with AntiThrombin III to interfere with coagulation.
81
AntiThrombin III collects/distrupts which factors to disrupt clot formation?
12, 11, 10, 9, and 2
Which influences Factor 2 (prothrombin)
82
Plasminogen is activated to Plasmin by?
tPA (tissue plasminogen activator) and Urokinase
83
What are 2 important fibrinolytic mediators that stop the process of fibrinolysis once a clot has been digested / fully broken down?
Alpha-Antiplasmin and Tissue Plasminogen Activator Inhibitor
84
How and where does Aspirin and NSAIDS affect coagulation?
Within the phospholipid bilayer. Aspirin (irreversible) and NSAIDS (reversible) inhibit cyclooxygenase (COX). COX converts arachidonic acid to prostaglandins which in turn releases/excites Thromboane A2, responsible for platelet aggregation.
So - Aspirin and NSAIDS decrease platelet function
85
Plt levels: 100,000 , 50,000 , and 20,000 what is the risk of spontaneous bleeding
Plt levels under 100,000 is considered thrombocytopenic.
50,000 - spontaneous bleeding is rare but you should suspect prolonged bleeding under surgical conditions
20,000 - spontaneous bleeding is likely to occur. Considered a critical level.
86
What are 2 key functions of vWF
1. Mediates adhesion of platelets at sites of vascular injury
2. Binds and stabilizes factor 8. Carries inactivated factor 8 in plasma.
87
Lab values expected in DIC
Reduced platelet count : At least less than 100.
Decreased Fibrinogen: Less than 1g/L
Increased PT/PTT: At least greater than 3sec
Increased D-Dimer:
88
Pt is in DIC and needs to go to OR. What would you give?
FFP
Platelets
In some cases Cryo or AntiThrombin III
89
Your patient has an X-Linked coagulation disorder and needs surgery. What can you give them if indicated?
Hemophilia A - Factor 8 deficient
Hemophilia B - Factor 9 deficient
Factor 8 concentrate can be given prior to surgery
Factor 7 can be given intraoperatively
Desmopressin can also be given in increase vWF and Factor 8 plasma levels
90
A Sickle Cell Crisis can be triggered by?
Hypoxemia
Hypothermia
Infection
Dehydration
Venous Stasis
Acidosis
91
What is one of the most common surgeries needed by people with Sickle Cell Disease and why?
Cholecystectomy for gall stones.
Because of excess bilirubin resulting from the rapid breakdown of sickle erythrocytes
92
What are some intraoperative management strategies for patients with sickle cell?
Adequate hydration
Avoid hypoxemia
Maintain normothermia
Maintain normal-acid base balance
Provide adequate perioperative pain management
Caution using vasoocclusive devices such as tourniquets
93
What is Heparin Induced Thrombocytopenia (HIT)?
An immune response to herparin that can progress to severe thrombosis, amputation, and in some cases death
94
Describe HIT type I
(immune or nonimmune, onset, degree of thrombocytopenia, tx, long term effects)
-Nonimmune Mediated. Thrombocytopenia is mediated by direct heparin-induced platelet aggregation
-Onset is typically 1-4 days after start of heparin therapy
-Mild thrombocytopenia (<100,000)
-Thrombocytopenia often resolves even with continued heparin therapy
-typically occurs with high-dose heparin administration
-Not associated with thrombosis and serious sequelae
95
Describe HIT type II
(immune or nonimmune, onset, degree of thrombocytopenia, tx, long term effects)
- Immune mediated. thrombocytopenia mediated by heparin, platelet factor 4, and IgG expression
- Onset usually 5-14 days after start of heparin therapy
-Severe thrombocytopenia (<60,000)
- Thrombocytopenia does not resolve spontaneously. must stop heparin.
-Associated with thrombosis and serious sequelae
96
What are 2 anti-platelet drugs whose MOA are COX-1 nonspecific inhibitors?
Aspirin (ASA) COX-1 Inhibitor (irreversible)
NSAIDS COX-1 inhibitor (reversible)
97
What are 2 anti-platelet drugs whose MOA are ADP receptor antagonist?
Clopidogrel
Ticagrelor
98
What are 3 anti-platelet drugs whose MOA are Glycoprotein IIb/IIIa receptor antagonists?
Abiximab
Eptifibate
Tirofiban
99
What anticoagulant medication is a Factor Xa indirect antagonist? (indirect - antithrombin cofactor)
What lab monitors?
Fondaparinux
Antifactor Xa assay
100
What 2 anticoagulant medication is a Factor IIa AND Xa indirect antagonist? (indirect - antithrombin cofactor)
What lab monitors? What is the reversal?
LMWH and Heparin (unfractionated)
LMWH - Antifactor Xa assay
*partial reversal with protamine
Heparin - aPTT
*Protamine
101
What anticoagulant drug has an MOA that is a Vitamin K epoxide reductase antagonist?
What lab monitors? What is the reversal?
Warfarin
PT
Vitamin K (phytonadione), FFP, PCC
102
What anticoagulant drug has an MOA that is a Factor IIb direct antagonist?
What lab monitors? What is the reversal?
Dabigatran (Pradaxa)
Dilute Thrombin Time
Idarucizumab
103
What 4 anticoagulant drugs have an MOA that is a Factor Xa direct antagonist?
What lab monitors? What is the reversal?
Rivaroxaban (Xarelto)
Apixaban (Eliquis)
Edoxaban
Betrixaban (Portola)
-Antifactor Xa Assay
-Andexanet alfa
104
What are 2 Fibrinolytic drugs whose MOA are Tissue Plasminogen Activators?
What lab values monitor?
What is the reversal?
t-PA
Streptokinase
(Tenecteplase could also be included)
PT/aPTT
-Antifibrinolytics
105
Some drugs have secondary anti-platelet activity. What are two Direct Thrombin Inhibitors that do that?
Bivalrudin
Dabigatran
106
What is the most common comordbidity in patients with SCD?
Asthma. Occurs in about 50% of SCD patients
