hemostasis Flashcards

Question

platelet aggregation is mediated by?

Answer 1

mediated by GpIIb/IIIa-receptor and fibrinogen → formation of a white thrombus composed of platelets and fibrin

Answer 2

- adhesion vs aggregation | - platelet-endothelium vs platelet-platelet

Answer 3

Platelet clot is reinforced by production of a fibrin clot, either by intrinsic or extrinsic pathway. it is the coagulation cascade

Answer 4

A part of the coagulation cascade that is initiated when collagen is exposed. Primarily consists of factors VIII, IX, XI, and XII. Activated mainly by thrombin. Impairment of this pathway results in bleeding disorders (e.g., hemophilia A and B). Hemostasis and bleeding disorders

Answer 5

A part of the coagulation cascade that is activated by injury to the endothelium. Consists of tissue factor (factor III) and factor VII. Impairment of this pathway results in bleeding disorders (e.g., factor VII deficiency).

Answer 6

or (factor III), which is present under the endothelium on fibroblasts, binds to and thus activates factor VII Factor VIIa and tissue factor form a complex (TF-FVIIa)* that activates factor X and factor IX.

Answer 7

Thrombin activates factors XI and factor VIII. Factor XIa activates factor IX Factors VIIIa and IXa form a complex* that activates factor X.

Answer 8

it is bound to vWF and is released during primary hemostasis. Activated by thrombin and acitvates factor X

Answer 9

A protein that is found in the cytoplasm of vascular endothelial cells, on the surface of fibroblasts in the subendothelium of blood vessels, and within leukocytes. Tissue factor is involved in the extrinsic pathway of the coagulation cascade. Damage to blood vessels results in the release of tissue factor, which binds to circulating factor VII and allows its activation. The complex of activated factor VII (VIIa) and tissue factor can then activate factor X of the common pathway in the coagulation cascade.

Answer 10

Factor XII is a coagulation cascade factor that activates the kallikrein system and leads to the production of bradykinin. Can be activated by bacterial endotoxins.

Answer 11

- -Factor Xa and factor Va form a complex* that cleaves prothrombin to thrombin (= factor II). - -Thrombin cleaves fibrinogen (factor I) into insoluble fibrin (factor Ia) monomers. - -Cross links of the fibrin network are stabilized by factor XIIIa → formation of a fibrin network → fibrin closely binds to the platelet plug, forming a stable fibrin clot (secondary or red thrombus)

Answer 12

The coagulation cascade requires the presence of calcium ions (factor IV)!

Answer 13

A helpful way of remembering the coagulation factors of the extrinsic pathway is 3 + 7 = 10. Factor III and factor VII form a complex to activate factor X of the common pathway.

Answer 14

A helpful way of remembering the coagulation factors of the common pathway is 1 x 2 x 5 = 10. Factors Xa and Va form a complex that cleaves prothrombin (II) to thrombin (IIa). Factor IIa then cleaves fibrinogen (I) into insoluble fibrin monomers (Ia).

Answer 15

a. thrombomodulin binds to thrombin and converts it from a procoagulant into an anti-coagulant via its ability to activate protein C. Protein C inhibits clotting by inactivating factors Va and VIIIa. Protein S (cofactor for protein C) b. tissue pathway factor inhibitor Directly inhibits tissue factor-factor VIIa and factor Xa activities.

Answer 16

forms the activated protein C complex together with its cofactor protein S (APC complex) → inhibition of factors Va and VIIIa → inhibition of coagulation cascade Produced in the liver; synthesis requires vitamin K Shorter half-life than the other coagulation factors dependent on vitamin K Clinical relevance: APC resistance; treatment with vitamin K antagonists

Answer 17

One of the most important physiological inhibitors of hemostasis. Degrades thrombin and other coagulation factors (factor IXa and Xa) and activates tissue plasminogen activator (tPA). Clinical relevance: The efficacy of antithrombin may be affected by various factors (it is increased by unfractionated heparin and decreased in states of impaired hepatic and kidney function.)

Answer 18

A serine protease found on endothelial cells of the blood vessels. Catalyzes the conversion of plasminogen to plasmin, which is the main enzyme responsible for clot breakdown. Recombinant tissue plasminogen activators (e.g., alteplase, reteplase, tenecteplase) are used as thrombolytics in patients with acute coronary syndrome, pulmonary embolism, or ischemic stroke.

Answer 19

--Tissue injury → release of factor XII , urokinase and tissue plasminogen activator (tPA) → Breakdown of plasminogen, leading to the formation of active plasmin → breakdown of fibrin by activated plasmin → Release of degradation products, including D-dimers --Regulation of fibrinolysis: tPA activity is reduced if tPA binds to plasminogen activator inhibitor (PAI).

Answer 20

fibrin degradation product released when plasmin cleaves crosslinked fibrin. Increased serum concentrations of D-dimer indicate recent intravascular coagulation and/or fibrinolysis (e.g., from deep vein thrombosis, pulmonary embolism, disseminated intravascular coagulation).

Answer 21

Once healing is initiated, clot dissolution via action of fibrinolytic system. Endothelial cells synthesize tissue type plasminogen activator (t-Pa). • It cleaves plasminogen to form plasmin. Plasmin then cleaves fibrin to degrade thrombi. • Plasmin lyses clot form fibrinogen degradation products (such as D-dimer) • tPA is inhibited by Plasminogen Activator Inhibitor

Answer 22

Thrombomodulin functions as a cofactor in the thrombin-induced activation of protein C in the anticoagulant pathway by forming a 1:1 stoichiometric complex with thrombin. This raises the speed of protein C activation thousandfold.

Answer 23

factor XII | activated by negatively charged surfaces (glass)

Answer 24

hemophilia C

Answer 25

hemophilia B

Answer 26

The intrinsic pathway is activated by exposing factor XII to thrombogenic surfaces whereas extrinsic pathway requires exogenous trigger (provided originally by tissue extracts).

Answer 27

* Initiation – TF (thromboplastin) + Factor VII * VIIa – high affinity bind with TF * Results in activation of IX and X * Xa with its cofactor Va generates a small burst of thrombin * Not sufficient to generate large amounts of fibrin * Thrombin back-activates to amplify process

Answer 28

* Thrombin burst back-activates FV, FVIII, FXI * FXIa activates FIX * FIXa complexes with FVIII (Haemophilia A) * FIXa-FVIIIa – tenase(intrinsic) complex * Tenase complex further activates FX * FXa complexes with FVa – Prothrombinase complex * Explosive generation of thrombin leading to clot formation * These reactions occur on a phospholipid bearing surface – cell membrane * In general reactions take place on the surface of activated platelets * The product of one reaction becomes the enzyme in the next reaction

Answer 29

In coagulation, the procoagulant protein factor X can be activated into factor Xa two ways; extrinsically or intrinsically. The activating complexes are called tenase.

Answer 30

Extrinsic tenase complex is made up of tissue factor, factor VII, and Ca2+ as an activating ion. Intrinsic tenase complex contains the active factor IX (IXa), its cofactor factor VIII (VIIIa)

Answer 31

1. activated in the case of tissue injury 2. is only factor seven (VII) which gets activated by tissue factor 3. Tissue factor then that activates factor 10 4. Factor 10 activates factor 5 5. Factor 5 activates factor 2 which is prothrombin(the inactive name of thrombin is prothrombin). 6. Factor 2a then activates factor 1 which is fibrin (the inactive name of fibrin is fibrinogen).  So both pathways aim to eventually activate factor 10 which then activates 5, 2, and 1 to form fibrin at the end

Answer 32

1. Factor 12 activates factor 11. 2. Factor 11 activates factor 9. 3. Factor 9 then form an active complex with factor 8 called the tenase complex. 4. That complex activates factor 10. 5. Factor 10 activates factor 5. 6. Factor 5 activates factor 2 which is thrombin(the inactive name of thrombin is prothrombin). 7. Factor 2 then activates factor 1 which is fibrin (the inactive name of fibrinogin is prothrombin).

Answer 33

both pathways aim to eventually activate factor 10 which then activates 5, 2, and 1 to form fibrin at the end

Answer 34

* Prothrombin Time (PT) * Activated Partial Thromboplastin Time (APTT) * Fibrinogen * D-Dimer

Answer 35

An assay that evaluates the extrinsic and common pathways of the coagulation cascade (measures activity of factors I, II, V, VII, and X). Used to evaluate coagulation disorders and to monitor the effect of warfarin. The normal range is 11–15 seconds.

Answer 36

* It is used to monitor the functioning of the extrinsic and the common pathways. * Sample collected + citrate added (anticoagulant) - centrifuge to separate platelet-poor plasma * Add Ca2+, phospholipid + thromboplastin + measure time to form fibrin clot (in secs) at 37°C * Normal PT is 12-15 seconds.

Answer 37

Ca2+, phospholipid + thromboplastin

Answer 38

I, II, V, VII, and X

Answer 39

``` Liver disease Vitamin K deficiency Warfarin Rivaroxaban* Low Fibrinogen ```

Answer 40

vit K is important for synthesis of factors X, IX, VII, II (1972), so as you see severe deficienc of vit K will prolong also PTT because factors invloved in common pathway are also affected (factor VII has the shortest half-life so affected first)

Answer 41

A vitamin K antagonist that inhibits hepatic epoxide reductase, thereby blocking synthesis (recycling) of the active, reduced form of vit. K. Without reduced vit. K, γ-carboxylation of glutamate residues cannot occur, which reduces the production of active coagulation factors II, VII, IX, and X, as well as anticoagulatory proteins C and S. Typically administered in patients with artificial heart valves, increased risk of deep vein thrombosis and pulmonary embolism, and/or valvular A-fib.

Answer 42

An assay that evaluates the intrinsic and common pathways of the coagulation cascade (measures activity of factors XII, XI, X, IX, VIII, V, II, and I). Used to evaluate coagulation disorders and to monitor the effect of heparin. Normal range is 25–40 seconds.

Answer 43

Fibrinogen, II, V, VIII, IX, X, XI, XII

Answer 44

Activated partial thromboplastin time (aPTT) • It is used to monitor the functioning of the intrinsic and the common coagulation pathways. • Normal aPTT is 24-38 seconds. • Platelet poor plasma at 37°C • Coagulation activated by kaolin calcium added  time taken for clot to form is recorded

Answer 45

VWF deficiency Liver Disease Low Fibrinogen Lupus Anticoagulant

Answer 46

because VWF carries factor VIII in blood!!!!!!!!!!!! exam question

Answer 47

--Measures the time it takes for fibrin polymers to form after adding thrombin --Only common pathway Fibrinogen --Formation of fibrin polymers

Answer 48

adequate fibrinogen levels.

Answer 49

Detect fibrinogen deficiency | Monitoring of heparin therapy and fibrinolytic therapy (alternative for aPTT)

Answer 50

Fibrin degradation products (FDPs)= D-dimer • They are used to assess the fibrinolytic activity and they are increased in disseminated intravascular coagulation (DIC), indicating fibrinolysis. Thrombin converts fibrinogen to fibrin. Fibrin monomers polymerize. Factor XIII forms a fibrin clot by linking 2 D-domains. Plasmin cleaves fibrin to produce D-dimers. • Useful test in excluding venous thrombosis- high negative predictive value NB: does not have a high positive predictive value (can be elevated for many reasons such as inflammatory disorder as well as thrombosis) • The normal value increases with age

Answer 51

False Useful test in excluding venous thrombosis- high negative predictive value NB: does not have a high positive predictive value (can be elevated for many reasons such as inflammatory disorder as well as thrombosis)

Answer 52

DIC, also called consuption couagulopathy, it is consumpted by fibrin cloths

Answer 53

An orally administered anticoagulant that directly and selectively inhibits factor Xa. it is used to treat deep vein thrombosis and pulmonary emboli and prevent blood clots in atrial fibrillation and following hip or knee surgery.

Answer 54

A storage granule found in endothelial cells. Contains von Willebrand factor and selectins (e.g., P-selectin).

Answer 55

platelet alpha-granules and Weibel Palade bodies

Answer 56

* Contains binding sites for fibrinogen (factor I), collagen and platelets (GP1b) * After vascular injury vWF binds to the exposed collagen – become unwound exposing more binding sites and binds fibrinogen and platelets

Answer 57

Autosomal Dominant

Answer 58

menstrual bleeding or peripartum bleeding

Answer 59

- -Mostly asymptomatic - -Symptomatic patients: 1) Ecchymosis (esp. mucosal hemorrhages) → from the reduced half-life of factor VIII 2) Petechial hemorrhages in severe cases → caused by impaired platelet aggregation 3) Other symptoms include epistaxis, gingival bleeding, menorrhagia, GI bleeding, and excessive bleeding during surgical procedures.

Answer 60

1) Prolonged bleeding time and sometimes prolonged activated partial thromboplastin time (aPTT) 2) ↓ Factor VIII levels 3) vWF-specific measurements - --Quantitative assessment by vWF antigen assay: ↓ factor levels - --Qualitative assessment by a collagen or glycoprotein Ib binding assay, or a ristocetin cofactor activity assay - Ristocetin normally activates vWF to bind to glycoprotein Ib - Failure of aggregation with a ristocetin assay or a ristocetin cofactor level < 30 IU/dL is considered definitive for vWD

Answer 61

An antibiotic used for platelet aggregation tests. Activates von Willebrand factor to bind glycoprotein Ib, thereby inducing platelet aggregation. Failure of aggregation occurs in conditions such as von Willebrand disease and Bernard-Soulier syndrome.

Answer 62

- -Recombinant von Willebrand factor (rVWF) concentrate - -Desmopressin: Stimulates vWF release from endothelial cells. - -Other treatment options: factor VIII concentrates ; oral contraceptives in cases with menorrhagia; antifibrinolytic drugs (i.e., aminocaproic acid, tranexamic acid) - -Avoid aspirin, NSAIDS, and intramuscular injections

Answer 63

* Type 1- partial deficiency (Autosomal dominant) * Type 2- variety of defects in multimers – qualitative defect * Type 3 – virtually absent vWF (mimics haemophila A, autosomal recessive)

Answer 64

False It is of no use in complete vWF deficiency (type 3) because it only causes the release of stored vWF. It may be used in type 1 and in some patients with type 2.

Answer 65

X-linked recessive so mainly boys are affected

Answer 66

is based on Factor VIII level • <1% severe • 1-5% moderate • 6-50% mild

Answer 67

Hemophilia B

Answer 68

no or mild symptoms (due to skewed X-inactiation)

Answer 69

An X-linked recessive disease that results in the deficiency of factor VIII. Most often presents in boys with recurrent episodes of epistaxis, bruising, and/or hemarthrosis. Lab studies show normal platelet counts, BT, PT, but prolonged aPTT.

Answer 70

* Factor VIII is made predominantly in the liver * Circulates bound to vWF – inactive in this form * Tissue injury occurs – then dissociates from VWF and becomes active – FVIIIa * FVIII interacts with Factor FIX * Dysfunctional Factor VIII or reduced amount of FVIII * Factor VIII gene Xq28

Answer 71

1) The severe variant of hemophilia A is caused due to an inversion of the intron 22 sequence involving the X chromosome that completely abolishes the synthesis of factor VIII (50% of severe Haemophilia A cases). Other mutations include deletions and point mutations. 2) A rarer mechanism for Factor VIII deficiency is the development of antibodies (inhibitors) to Factor VIII – accelerates clearance of Factor VIII from circulation.

Answer 72

1) Spontaneous or delayed onset bleeding (joints, muscular and soft tissue, mucosa) in response to different degrees of trauma - -Repeated hemarthrosis → joint destruction 2) Further sites/symptoms of hemorrhage: - -CNS (e.g., headache, neck stiffness) - -Gastrointestinal tract (e.g., melena, hematemesis) - -Genitourinary system (e.g., hematuria) - -Oral mucosa bleeding, epistaxis, excessive bleeding following small procedures (e.g., dentist procedures) - -Female carriers may show mild symptoms.

Answer 73

1) Screening - -Prothrombin time: normal - -Platelet count: normal - -Activated partial thromboplastin time (aPTT): usually prolonged 2) If aPTT prolonged → mixing study 3) If mixing study is positive (or if patient/family history are strongly positive) → quantitative assessment of factor activity levels

Answer 74

First, measure the aPTT of the patient's blood. Then, mix the patient's plasma with external plasma that is known to contain sufficient clotting factors and measure the resulting aPTT. If the patient suffers from hemophilia, the aPTT will be corrected in the sample with the external plasma.

Answer 75

1) Substitution of clotting factors - -Mild or moderate hemophilia: when needed (e.g., trauma or surgery) - -Severe hemophilia: prophylactic (additional substitution may be needed in, e.g., trauma) 2) Desmopressin - -Indication: mild hemophilia A - -Synthetic analog of vasopressin 3) Antifibrinolytic therapy (e.g., ε-Aminocaproic acid, tranexamic acid): used in addition to factor substitution (e.g., if surgery is performed in the oral cavity)

Answer 76

Antifibrinolytic therapy is contraindicated in patients with hematuria (usually macroscopic) due to the formation of blood clots in the urinary tract.

Answer 77

VIIa, | to bypass factor VIII activation of X

Answer 78

aspirin, NSAIDs, clopidogrel,

Answer 79

A synthetic lysine analog and inhibitor of plasminogen with antifibrinolytic action. Indicated in the treatment of excessive blood loss from major trauma, menorrhagia, acute AUB, postpartum bleeding, surgery, dental procedures, and epistaxis. Side effects include changes in color vision, thromboembolic events, and anaphylaxis. • Very cheap and useful medication • Given IV or PO • Lysine analog • Binds to lysine receptors on plasminogen • Reduces conversion of plasminogen to plasmin • Reduces degradation of fibrin • Reduces mortality if given <3 hours of major trauma • NB – relatively contraindicated in haematuria or prior thrombosis

Answer 80

there is an ability to form an adequate platelet plug

Answer 81

Thrombocytopenia is defined as counts < 100,00 uL, but spontaneous bleeding does not occur until platelet numbers < 20,000 uL. Counts between 20,000-50,000 uL can exacerbate posttraumatic haemorrhage. Most spontaneous bleeds involve small vessels of the skin and mucous membranes.

Answer 82

- -decreased productiondue to ineffective megakaryopoiesis (eg. HIV, myelodysplastic syndromes) or to generalised bone marrow disease that compromises megakaryocyte number (aplastic anaemia, disseminated cancer so secondary to cancer). - decreased survival due to increased consumption(DIC), or to immune-mediated platelet destruction (immune complex deposition on platelets). - sequestration in red pulp of enlarged spleen - dilution due to massive transfusions

Answer 83

count is <30 x 109/L • Spontaneous bleeding rare unless platelet count <1010/L • Other factors may alter this: Aspirin, Anticoagulants, NSAIDs, Trauma, Renal Failure, Liver Failure

Answer 84

- an immune-mediated attack (usually IgG antiplatelet antibodies) against platelets leading to decreased platelets (thrombocytopenia). This results in petechiae, purpura (bruises), and a bleedingdiathesis (e.g., hematomas). - classically presents with a petechial rash – often lower limbs – or with mucocutaneous bleeding

Answer 85

- -Primary (acute) ITP: inciting factors such as viral infection that causes an autoimmune reaction. It resolves over weeks with little or no intervention - -Secondary ITP: associated with lymphoma, leukemia, SLE, HIV, HCV. Usually seen in women in their childbearing years and can be the first manifestation of systemic lupus erythematosus (SLE).

Answer 86

antiplatelet antibodies against platelet antigens such as GPIIb-IIIa and GPIb-IX (type II hypersensitivity reaction). The antibodies are made in the spleen, and the platelets are destroyed peripherally in the spleen by macrophages.

Answer 87

Lab studies usually show decreased platelet count and prolonged bleeding time but normal prothrombin time and partial thromboplastin time. Peripheral bloodsmear shows thrombocytopenia with enlarged immature platelets (megathrombocytes). Bone marrow biopsy shows increased numbers of megakaryocytes with immature forms.

Answer 88

False | Only BT as it does not involve coagulation cascade

Answer 89

Treatment is corticosteroids, which decrease antibody production; immunoglobulintherapy, which floods Fc receptors on splenic macrophages; and/or splenectomy,

Answer 90

HIV and HCV

Answer 91

* F>M * Onset in adulthood - 30s-40s * Incidence 1/10,000 * Isolated thrombocytopenia in a well patient * Normal Hb and WCC count * Asymptomatic apart from bleeding symptoms * May arise secondary to infection (HIV), Drugs (quinine), coexisting autoimmune disease (SLE), lymphoma, immunodeficiency syndromes (CVID) * Bone marrow morphology is normal or may show increased megakaryocytes * Autoimmune disorder – antiplatelet antibodies are present in most cases * Treatment not indicated unless platelets <20-30*9/L

Answer 92

Rituximab-kills B cells--no antibody production against platelets • Treated with immunosuppression • Steroids • Intravenous immunoglobulin • Rituximab • Splenectomy results in longterm remission in about 60-70% of cases

Answer 93

• Aspirin • Clopidogrel • Warfarin • DOACs 1. Anti-X agents – apixaban, rivaroxaban, edoxaban 2. Direct-thrombin inhibitors - dabigtran

Answer 94

A P2Y12 receptor antagonist that blocks platelet aggregation. It is used in the treatment of acute coronary syndrome and peripheral arterial disease as well as in the prevention of ischemic stroke (ADP usually binds to P2Y12 receptors, leading to activation of Gp IIb/IIIa receptors and subsequent platelet aggregation.)

Answer 95

* Primary treatment of venous thrombosis * Prevention of stroke and systemic thrombo-embolism * 70% - Atrial Fibrillation * 20% treatment of and prevention of recurrence of venous thrombosis * 10% other – valvular heart disease/replacement, peripheral vascular disease

Answer 96

* Major Bleeding – approx 2% of patients/yr– hospitalisation for transfusion, procedure or >2g drop in Hb * Minor bleeding – e.g. epistaxis – 10-15% per year * Highest mortality – ICH (Intracranial Haemorrhage) – 50% - approx.. 10-20% of all major bleeds * Latest data suggests lower ICH rate with newer OACs (DOACs) over warfarin * Possible increased risk of GI bleeding with DOACs

Answer 97

* ApiXaban, RivaroXaban, EdoXaban (all contain Xa in the name!!) * Oral – Apixaban BD, others OD * Short half-lives – 12-14 hours * Renal route of excretion – therefore caution and dose adjustment in renal impairment * Concentration affected by CYP inhibitors/inducers * Rivaroxaban prolongs PT * Routine monitoring not available

Answer 98

in cases of overdose, there is no antidote

Answer 99

NO (vs heparin or warfarin) studies have demonstrated a correlation between the levels of rivaroxaban and PT through inhibition of factor Xa, but not to the same extent as warfarin.

Answer 100

``` The most common form of drug interaction results from the induction of the cytochrome P450 enzyme system. CYP induction increases the rate of metabolism of the substrate, while CYP inhibition decreases it Common CYP inducers are --prednisolone --Carbamazepine --Rifampicin --St. John's Wort --Griseofulvin --Isoniasid --antiepileptic drugs ```

Answer 101

* Dabigatran * Oral agent - BD dosing * Renal excretion – needs dose adjustment/caution in renal impairment * Prolongs Thrombin Time * Variably prolongs APTT but not PT

Answer 102

no, | prolong aPTT

Answer 103

* Vitamin K antagonist (coumarins) * Warfarin inhibits Vitamin K epoxide reductase(VKORC) – required to form active Vitamin K * Prevents gamma-carboxylation of glutamic acid residues of Factors II, VII, IX, X * Also inhibits production of anticoagulant proteins – proteins C and S * Long-half life – 2-3 days * Takes 4-5 days to reach therapeutic level – oral – OD * Dose adjusted according to a blood test called INR – International Normalised Ratio * NB – Teratogenic – absolutely contraindicated in the first trimester

Answer 104

Inhibit hepatic vitamin K epoxide reductase → ↓ hepatic synthesis (recycling) of the active, reduced form of vitamin K → ↓ γ-carboxylation of glutamate residues on coagulation factors II, VII, IX, and X

Answer 105

X, IX, VII, II (1972)

Answer 106

yes | Also inhibits production of anticoagulant proteins – proteins C and S

Answer 107

False Long-half life – 2-3 days • Takes 4-5 days to reach therapeutic level – oral – OD

Answer 108

``` vit K (takes days for effect) PCC (prothrombin con=mplex concentrate) forimmediate reveral of bleeding ```

Answer 109

Idarucizumab | A monoclonal antibody that is used to reverse the effects of the anticoagulant dabigatran.

Answer 110

tranexamic acid, PCC and andexanet

Answer 111

A modified, inactive form of human factor Xa that binds to factor Xa inhibitors, such as rivaroxaban and apixaban, to reverse their anticoagulant effects (e.g., in patients who have life-threatening or uncontrolled bleeding). Also inhibits tissue factor pathway inhibitor to increase thrombin generation.

Answer 112

A condition characterized by systemic activation of the clotting cascade, platelet consumption, and subsequent exhaustion of clotting factors that leads to widespread thrombosis and hemorrhage. Often associated with trauma, shock, and sepsis.

Answer 113

True It is a secondary complication in a variety of diseases. It is triggered by two main mechanisms: 1. Release of tissue factor or thromboplastic substances into circulation 2. Wide-spread endothelial injury

Answer 114

Thromboplastic substances can be derived from: placenta/amniotic fluid/ damaged tissue following trauma, burns, surgery.

Answer 115

In sepsis, bacterial endotoxins activate monocytes to release TNF-a -- activation of clotting system and inhibition of coagulation control.

Answer 116

Endothelial injury initiates DIC by causing tissue release factor from endothelial cells, promoting platelet aggregation and activating intrinsic coagulation pathway by exposing subendothelial connective tissue.

Answer 117

Acute Promyelcytic Leukemia due to release of procoagulant activity from leukemic cells

Answer 118

Venom may contain thrombogenic enzymes that promote the formation of a fibrin clot, which in turn activates plasmin and results in consumptive coagulopathy.

Answer 119

– Thrombin(procoagulation) | – plasmin(fibrinolysis)

Answer 120

– an acute hemorrhagic disorder – an indolent, subacute thrombotic disorder • Not a primary diagnosis • Secondary phenomenon The clinical features of DIC may appear acutely (e.g., following trauma, sepsis), or may appear subacutely (e.g., DIC following malignancy)!

Answer 121

1) Thrombocytopenia → ↑ bleeding time 2) ↑ Markers of fibrin breakdown (D-dimer, or FDP) 3) ↑ PT and APTT 4) ↓ Fibrinogen levels 5) ↓ Antithrombin 6) ↓ Hematocrit 7) Schistocytes (In the case of DIC, schistocytes (fragmented erythrocytes) are seen in association with microangiopathic hemolytic anemia.)

Answer 122

Thrombus formation and subsequent inflammatory response in a superficial or deep vein. 1. Superficial thrombophlebitis 2. Deep vein thrombosis 3. Pulmonary embolism - Deep vein thrombosis is the commonest cause of pulmonary thromboembolism. - The thrombi propagate in direction of blood flow (more common in lower extremity).

Answer 123

1. Endothelial damage (changes in vessel wall) - exposes endothelium to promote hemostasis 2. Venous stasis (reduced/altered blood flow) - immobilization (post-MI, CHF, stroke, post-operative) inhibits clearance and dilution of coagulation factors 3. Hypercoagulability (alterations in blood constituents- prothrombotic changes)

Answer 124

True | - inherited or acquired (age/surgery/trauma/neoplasms) or idiopathic

Answer 125

* DVT: PE – 2:1 | * PE fatal in approximately 5-10% of cases within 1 month of diagnosis and DVT 2.5-5%

Answer 126

* DVT – pain, swelling, erythema,+ Homan sign | * PE – shortness of breath, chest pain, tachycardia, tachypnoea, haemoptysis

Answer 127

Immobility travel trauma surgery

Answer 128

``` Cancer age pregnancy and OCPs genetic thrombophilia APS trauma myelophroliferative disorders ```

Answer 129

A scoring system used to estimate the risk of deep vein thrombosis (DVT). Includes medical history (presence of active cancer, history of previous DVT), history of immobilization (paralysis or recent immobilization of a lower extremity, recent history of major surgery of remaining bedridden), and clinical symptoms (localized tenderness along the deep venous system, leg swelling, asymmetrical calf swelling, unilateral pitting edema, and presence of collateral, non-varicose superficial veins).

Answer 130

The hereditary thrombophilias are a group of inherited conditions that predispose to thrombosis. Examples are protein C, protein S, and antithrombin resistance or deficiency

Answer 131

An inherited or acquired state in which an individual is predisposed to forming blood clots. This most often manifests as recurrent deep vein thromboses or pulmonary emboli. Etiologies include conditions of inherited thrombophilia (e.g., factor V Leiden mutation), malignancy, pregnancy and the puerperium, various drugs (e.g., oral contraceptives, tamoxifen), and immobilization.

Answer 132

- -Factor V Leiden (most common genetic cause of --hypercoagulability in the white populations) - -Protein C deficiency - -Protein S deficiency - -Antithrombin III deficiency - -Prothrombin G20210A mutation

Answer 133

- -Pregnancy - -Advanced age - -Smoking - -Obesity - -Surgery - -Immobilization - -Trauma - -Malignancy (especially adenocarcinoma) - -Antiphospholipid syndrome - -Nephrotic syndrome - -Oral contraceptive pills (OCPs)/hormone replacement therapy (HRT) - -Systemic lupus erythematosus (SLE) - -Heparin-induced thrombocytopenia

Answer 134

1) reduce risk factors (smoking, OCPs) 2) anticoagulation - -heparin+warfarin - -new anticoagulants (anti-Xa or thrombin inhibotors) - -3-6 months if provoked

hemostasis Flashcards

(171 cards)