Blood Clotting

Thrombus

Is a blood clot that forms in an unbroken vessel. A large ___ may block blood flow, causing tissue death.

Embolus

Is a blood clot that forms then breaks away and floats freely in the blood vessels. An ___ may then lodge in a capillary and block blood flow.

Bleeding Time

Test used? - Reference Range: 3-9 min - Abnormalities indicated: Abnormal platelet function - Common cause of disorder: Aspirin, uremia, von Willebrand disease

VIII or IX

The bottom line is: you need both the intrinsic and extrinsic pathways to form fibrin in vivo. If you don't have factors ___, you can't utilize the intrinsic pathway - and you'll have a very hard time forming fibrin!

Tissue damage, Collagen

The extrinsic pathway is triggered by ____, while the intrinsic pathway is triggered by ___

Factor 10 (Stuart Factor)

The intrinsic and extrinsic pathway both merge at what factor?

Hemostasis

The process of blood clotting

Intravenous, Clotting Factors

The treatment for hemophilia is ___ injection of ____ through donated plasma and synthetic clotting factors.

B) Glutamate

The vitamin K clotting factors 2, 7, 9, 10 carboxylate ___ residues. *Might ask what factors are activated by vitamin K, think 1972. A) Aspartate B) Glutamate C) Both D) None of the above

8 * It also uses desmopressin, which releases von willebrand factor. Be able to discern between hemophilia and von willebrand!

Von willebrand factor carries which factor?

Vitamin K

Warfarin is an antagonist of ____ and therefore inhibits factors 2,7,9,10 affecting the extrinsic pathway.

1. Injury to blood vessel or build-up of fatty plaques 2. Poor blood circulation

What are 2 causes of thrombus?

Prolonged bleeding even from minor injuries Excessive bruising Bruised and swollen joints Excessive clumsiness and falling

What are the 4 symptoms of hemophilia?

• Vitamin K antagonists (in vivo) eg Warfarin • Calcium chelators • EDTA (Ethylenediaminotetraacetic acid) • Citrate • Oxalate

What are the 5 Non-physiological inhibitors of coagulation?

Immobility

What increases the risk of deep vein thrombus in legs?

Thromboplastin Prothrombin Thrombin Fibrin **Remember Thromboplastin --> Fibrin & This is a simplified overview of the clotting cascade

When there's injury to the blood vessel, one of the things that can happen is ___ being released, which interacts with PLATELET FACTOR 3 & CALCIUM to form ____ activator. This activator converts prothrombin to thrombin. ___ converts fibrinogen into long, insoluble proteins called ____, which forms a mesh that traps erythrocytes and platelets, pulls the edges of the broken vessel together, and forms a clot.

Constriction

When there's injury to the blood vessel, one of the things that can happen is damage to smooth muscles of the blood vessel and stimulation of pain receptors, which leads to blood vessel spasms, causing ____ of the blood vessel

Collagen, Platelets

When there's injury to the blood vessel, one of the things that can happen is exposure to ___ fibers on the vessel. This leads to activation of ____ that stick together and secrete serotonin, ADP, and thromboxane A2.

Endothelial Cells

____ protect the body from clotting and line the vessels. Are thromboresistant in nature. They express thrombomodulin and heparin sulfate to keep inappropriate thrombi from forming. They also release tissue plasminogen activator and urokinase in the presence of thrombin shut off the coagulation cascade in the presence of IIa (thombin

Xa

As as soon as we make a little ___ and that (along with the aptly-named tissue factor pathway inhibitor) turns off the extrinsic pathway! A little thrombin is formed, though, before the pathway gets turned off - and that thrombin kicks off the intrinsic pathway (the other side of the cascade, with factors VIII and IX). Fibrin formation then proceeds along this pathway until it's no longer needed.

Fibrinolysis

As soon as the injury is healed clot dissolution starts, to restore the normal flow of blood in a process called?

Tissue Factor Pathway Inhibitor (TFPI)

As soon as thrombin is formed, this is released and immediately inhibits the extrinsic pathway

Subendothelium

Beneath the endothelium. Are thrombogenic in nature. Express von Willebrand Factor (vWF), collagen, and tissue factor to kick off the coagulation cascade.

Extrinsic

Clotting initially begins along the ___ pathway.

Plasma D-Dimers

Cross-linked fragments containing D-Dimer epitopes

Tissue plasminogen activator (t-PA) & Urokinase

During Fibrinolysis, plasminogen is converted to its active form plasmin by 2 distinct Plasminogen Activators (PAs): ____ from injured endothelial cells & ____ from Kidney endothelial cells and plasma

Plasmin

During Fibrinolysis, plasminogen is converted to its active form?

Serotonin, ADP, thromboxane A2

During the process of hemostasis, after there's injury to the vessel, 3 things can happen, the damage to smooth muscles and exposed collagen fibers both converge at 3 secreted chemicals from platelets which are?

1. Thrombomodulin 2. Heparin Sulfate 3. Tissue Plasminogen 4. Urokinase

Endothelial cells - line the vessels. Are thromboresistant in nature. They express ___ & ___ to keep inappropriate thrombi from forming. They also release ___ activator & ___ in the presence of thrombin shut off the coagulation cascade in the presence of IIa (thombin).

A) Thromboresistant, Thrombogenic

Endothelial cells are ___, while subendothelium is ___. A) Thromboresistant, Thrombogenic B) Thrombogenic, Thromboresistant

Vitamin-K dependent coagulation components

Factors X, IX, VII, II, proteins C, S (mnemonic: 1972 [10, 9, 7, 2]). These are the?

1: Fibrinogen 2: Prothrombin 3: Thromboplastin/Tissue factor 4: Calcium 5: Labile Factor 6: Not been proved

Factors involved in blood clotting: 1: 2: 3: 4: 5: 6: *Says we don't have to memorize this, but will show us how to use it, so we have to understand most

7: Stable factor 8: Antihemophilic 9: Christmas factor 10: Stuart factor 11: Plasma thromboplastin antecedent 12: Hageman factor 13: Fibrin stabilizing factor

Factors involved in blood clotting: 7: 8: 9: 10: 11: 12: 13: *Says we don't have to memorize this, but will show us how to use it, so we have to understand most

1. damaged 2. Clot 3. 3-6 minutes

Hemostasis: - Occurs when small blood vessel (capillary) is ___ - ___ seals the blood vessel until it regenerates - Occurs in just ____

Prothrombin Time (PT): Prolonged Partial Thromboplastin Time(PTT): Prolonged Bleeding Time: Prolonged Platelet count: Unaffected

In Afibrinogenemia: Prothrombin Time (PT): Partial Thromboplastin Time(PTT): Bleeding Time: Platelet count:

Prothrombin Time (PT): Prolonged Partial Thromboplastin Time(PTT): Prolonged Bleeding Time: Prolonged Platelet count: Low

In DIC (Disseminated intravascular coagulation): Prothrombin Time (PT): Partial Thromboplastin Time(PTT): Bleeding Time: Platelet count:

Prothrombin Time (PT): Prolonged Partial Thromboplastin Time(PTT): Prolonged Bleeding Time: Unaffected Platelet count: Unaffected

In Factor 5 & 10 (V & X): Prothrombin Time (PT): Partial Thromboplastin Time(PTT): Bleeding Time: Platelet count:

Prothrombin Time (PT): Prolonged Partial Thromboplastin Time(PTT): Prolonged Bleeding Time: Prolonged Platelet count: Unaffected

In TPA/Streptokinase: Prothrombin Time (PT): Partial Thromboplastin Time(PTT): Bleeding Time: Platelet count:

Prothrombin Time (PT): Unaffected Partial Thromboplastin Time(PTT): Unaffected Bleeding Time: Prolonged Platelet count: Low

In Thrombocytopenia (decreased platelet number) IgG: Prothrombin Time (PT): Partial Thromboplastin Time(PTT): Bleeding Time: Platelet count:

Prothrombin Time (PT): Prolonged Partial Thromboplastin Time(PTT): Prolonged Bleeding Time: Unaffected Platelet count: Unaffected

In Vitamin K Deficiency/Warfarin Prothrombin Time (PT): Partial Thromboplastin Time(PTT): Bleeding Time: Platelet count:

Prothrombin Time (PT): Unaffected Partial Thromboplastin Time(PTT): Prolonged Bleeding Time: Prolonged Platelet count: Unaffected

In Von Willebrand Disease: Prothrombin Time (PT): Partial Thromboplastin Time(PTT): Bleeding Time: Platelet count:

Prothrombin Time (PT): Unaffected Partial Thromboplastin Time(PTT): Unaffected Bleeding Time: Prolonged Platelet count: Unaffected

In aspirin: Prothrombin Time (PT): Partial Thromboplastin Time(PTT): Bleeding Time: Platelet count:

Prothrombin Time (PT): Prolonged Partial Thromboplastin Time(PTT): unaffected Bleeding Time: unaffected Platelet count: unaffected

In early liver failure: Prothrombin Time (PT): Partial Thromboplastin Time(PTT): Bleeding Time: Platelet count:

Prothrombin Time (PT): Prolonged Partial Thromboplastin Time(PTT): Prolonged Bleeding Time: Prolonged Platelet count: Decreased

In end-stage liver failure: Prothrombin Time (PT): Partial Thromboplastin Time(PTT): Bleeding Time: Platelet count:

Prothrombin Time (PT): Unaffected Partial Thromboplastin Time(PTT): Prolonged Bleeding Time: Unaffected Platelet count: Unaffected

In hemophilia: Prothrombin Time (PT): Partial Thromboplastin Time(PTT): Bleeding Time: Platelet count:

Tissue Factor, VIIa

In our bodies, the thing that kicks off the clotting cascade is ___ "exposure, "which is not floating around in the blood normally - or at least, it isn't normally "visible" to the blood (it might be in little membrane fragments, but it's not active until it's needed). When you need to form a clot, it appears, and together with factor ___ (which happens to be just floating around in the blood) it converts factor X to Xa (which then converts prothrombin to thrombin, which converts fibrinogen to fibrin)

1) Vasoconstriction 2) Platelet plug formation 3) Coagulation of blood

In the process of hemostasis, three major events occur, all beginning the moment the vessel is damaged?

Prothrombin Time (PT): Unaffected Partial Thromboplastin Time(PTT): Unaffected Bleeding Time: Prolonged Platelet count: Unaffected

In uremia: Prothrombin Time (PT): Partial Thromboplastin Time(PTT): Bleeding Time: Platelet count:

Warfarin (Coumadin)

Inhibits vitamin-K reductase and effective levels of of vitamin-K dependent coagulation components. Will extend the PT.

Elevated

Is a Plasma D-Dimer elevated or decreased in thrombosis, embolism, and coagulation?

Prothrombin Time (PT)

Measures the function of the extrinsic pathway and the common pathway. Extended by warfarin.

Partial Thomboplastin time (PTT)

Measures the function of the intrinsic pathway and the common pathway. In vitro extension by heparin.

Platelets

One of the causes of thrombus is Injury to blood vessel or build-up of fatty plaques, Both create rough surfaces inside vessel, which may activate?

Clotting factors

Poor blood circulation, a cause of thrombus, may have accumulation of?

Heparin (drug)

Purified from animals. Increases the activity of ATIII. Will increase the aPTT in vitro.

Starts with prothrombin --> thrombin --> fibrinogen activates fibrin --> Calcium and active factor 13 makes the blood clot

Simply put, what is the common pathway steps of coagulation?

Tissue Factor 3 --> Factor 7 --> Factor 10 --> (Prothrombin -> Thrombin) --> (Fibrinogen -> Fibrin) --> by Factor 13 a clot is formed

Simply put, what is the extrinsic pathway steps of coagulation which is triggered by tissue damage?

XIIa & calcium activate XI --> IX --> (VIII) --> X

Simply put, what is the intrinsic pathway steps of coagulation which is triggered by collagen?

von Willebrand factor (vWF), Collagen & Tissue Factor *Tissue factor triggers blood clotting

Subendothelium - beneath the endothelium. Are thrombogenic in nature. Express ___, ___, & ___ to kick off the coagulation cascade.

Thromboxane A2 (TXA2)

Synthesis of it is initiated by activated platelets. It increases platelet activation and aggregation. Its synthesis is inhibited by aspirin/COX (cycloxygenase).

PT or International Normalized Ratio (INR)

Test used? - Reference Range: 12-16 s (PT) 1.0-1.3 (INR) - Abnormalities indicated: Extrinsic + Common Deficiency/Inhibition VII, X, V, II, I - Common cause of disorder:Liver disease, warfarin therapy, DIC

Thrombin Time (TT)

Test used? - Reference Range: 14-16 s - Abnormalities indicated: Deficiency/abnormal I, inhibition of II by heparin or FDPs - Common cause of disorder: DIC, Heparin therapy, fibrin clot therapy

APTT/PTT with Kaolin/ Kaolin Cephalin Clotting Time

Test used? - Reference Range: 23-31 s - Abnormalities indicated: Intrinsic + Common Deficiency/Inhibition XII, IX, VIII, X, V, II, I - Common cause of disorder:Liver disease, heparin therapy, VIII, IX, DIC

Fibrin Degradation Products (FDPs) or Fibrin Split Products (FSP)

Test used? - Reference Range: <10 mg/mL - Abnormalities indicated: Accelerated destruction of fibrinogen - Common cause of disorder: DIC (disseminated intravascular coagulation)

Heparin, Va and VIIIa

The 2 Physiological Inhibitors of Coagulation, Antithrombin III is activated by ___ & Activated Thrombomodulin Activates Protein C which inturn inhibits Factors ___

Plasmin

Thrombin also activates ___, which takes part in fibrinolysis, or the digestion of fibrin into fragments

Factor 12 (Hageman factor)

Through positive feedback, the extrinsic pathway can trigger the intrinsic pathway at its second step, so if there is a problem with factor ____, it won't affect the intrinsic pathway since there's a backup plan & doesn't cause bleeding because the second step kicks in.

Deep Vein Thrombosis Pulmonary Embolism Disseminated Intravascular Coagulation (DIC) Plasma D-dimers are elevated in these conditions

What 3 things do Plasma D-Dimers diagnose? & are the values increased or decreased in these situations?

Antithrombin III & Activated Thrombomodulin

What are the 2 Physiological Inhibitors of Coagulation?

• Lack of Factor VIII*(Hemophilia A) or Factor IX (Hemophilia B) • Recessive sex-linked trait (more common in men)

What are the 2 causes of hemophilia?

Tissue plasminogen activator (t-PA), Urokinase & Streptokinase

What are the 3 plasminogen activators?

Collagen

What is exposed to the blood that initiates a pathway to clot?

PT test *Think war veterans need PT

What screening procedure is used for the extrinsic and common pathways and for warfarin drug therapies?

3) Coagulation of blood

Which one takes the longest to occur? 1) Vasoconstriction 2) Platelet plug formation 3) Coagulation of blood

D) A & B

You actually need both the ___ pathways in your body. In a test tube, you can form fibrin along either pathway. But in the body, the pathways are intertwined in such a way that if you're missing something on either the extrinsic or intrinsic side, you won't be able to clot properly. A) intrinsic B) extrinsic C) common D) A & B E) B & C F) A& C