Unit 3 - Formative 10 D1

Front 1

Primary Location of Megakaryotes in Bone Marrow

Back 1

Close to sinus endothelial cells to expel platets directly into sinuses; platelets are fragments of the cytoplasm of megakaryocytes

Front 2

Function of Glycoproteoin Ib (GPIb)

Back 2

Platelet receptor for vWF; noncovalently associated with GP IX; complex is called GPIb/IX

Front 3

Function of Glycoprotein IIb/IIIa

Back 3

Major plasma membrane receptor for fibrnogen; hidden in resting platelets and has a low affinity for fibrinogen; when platelet is activated GpIIb/IIIa is converted to a high affinity binding form

Front 4

Structural Zone

Back 4

Comprised of microtubules + filaments/microfiliaments

Function is to mediate shape change when the platelet is activated

Front 5

Organelle Zone

Back 5

Contains granules filled with proteins for platelet function

Front 6

Alpha and Dense Granules

Back 6

Alpha: contain platelet growth factors
Dense: Serotonin for vasoconstriction

Front 7

Platelet derived agonists

Back 7

ADP, serotonin, platelet activating factor, thromboxane A2

Front 8

Nonplatelet derived agonists

Back 8

Collagen, thrombin, epinephrine

Front 9

How do platelets change in shape once activated?

Back 9

Discoid shape -> one with long projections emanating from the surface

Front 10

Thrombosis

Back 10

Pathologic counterpart of hemostasis; formation of blood clot within intact vessels

Front 11

Primary Hemostasis

Back 11

Platelets interact with injured blood vessel and one another to form a hemostatic plug; plug arrests bleeding but can be easily dislodged

Front 12

Secondary Hemostasis

Back 12

Coagulations factors recruit fibrin -> strands deposited on the platelet plug stabilizing it

Front 13

Fibrinolysis

Back 13

Dissolution of the clot

Front 14

Fibrinolysis

Back 14

Dissolution of the clot

Front 15

Arteriolar Vasoconstriction

Back 15

Transient event; cant main hemostasis

Front 16

Platelet Adherence and Activation

Back 16

Endothelial injury exposes extracellular matrix; platelet activation and adherence; platelets increase their surface area by changing shape; platelets release secondary granules which recruit additional platelets = formation o fplug

Front 17

Exposure of Tissue Factor

Back 17

Tissue factor + VII = invivo coagulation; formation of thrombin which creates fibrin meshwork

Front 18

Secondary Hemostasis

Back 18

Reinforces initial platelet plug

Front 19

Antiplatelet and Antithrombotic Endothelial Properties

Back 19

Protein S also produced by endothelium; cofactor for Protein C

Front 20

t-PA

Back 20

Protease that converts plasminogen into plasmin; plasmin cleaves fibrin

Front 21

Formatoin of Vascular Plug

Back 21

Glanzman Thrombasthenia; Bleeding disorder due to GP IIb/IIIa deficiency

Front 22

There are many blood coagulation proteins that need vitaminK

Back 22

Vit K needed for gamma carboxylation of glutamic acid residues; otherwise factors cant bind to the negatively charged phospholipid surfaces by way of calcium bridges

Front 23

X->Xa via extrinsic pathway

Back 23

The above illustration shows the conversion of factor X to factor Xa by way of the extrinsic pathway. Note that calcium ions hold the components together and are essential for the reaction. The activated factor Xa becomes the proteases for the following complex.

Front 24

Extrinsic vs Intrinsic cascade

Back 24

Extrinsic vs Intrinsic cascade

Front 25

Note common pathway

Back 25

Extrinsic and intrinsic pathways converge at common pathway
Factor X (K dependent); Xa activates prothrombin to thrombin

Front 26

Function of Thrombin

Back 26

Procoagulant, antithrombotic, roles in inflammation, roles in cellular proliferation

Front 27

Back 27

PA converts Plasminogen to plasmin; plasminogen binds fibrin and degrades it

Front 28

tPA

Back 28

Plasminogen + tPA -> Plasmin -> cleavage of fibrin mesh

Front 29

Thrombin Activatable Fibronolysis Inhibitor

Back 29

TFAI activated by thrombin/thrombomodulin complex; protects fibrin clot from lysis by inhibiting plasminogen

Front 30

Alpha 2 Antiplasmin

Back 30

Binds free plasmin to prevent fibrinolysis; however if plasmin is already bound to fibrin it's protected since its activation site is occupied

Front 31

Anti-coagulatoin

Back 31

Antithrombin inactivates factors II, VII, IX, X, and XI; ultimately inactivates thrombin

Herparin accelerates inhibition of target proteases; vascualr endothelium has 'heparin like' molecules

Front 32

Thrombomodulin

Back 32

Alters the activity of thrombin from procoagulant to anticoagulant

Front 33

Protein C (requires protein S)

Back 33

Activated protein C inhibits factor Va and VIIIa

Front 34

Tissue Factor Pathway Inhibitor

Back 34

TFPT binds and inhibits active site on Xa; this complex then reacts with VIIa in complex with tissue factor; inactivation of both proteases

Front 35

Thrombosis

Back 35

Due to endothelial injury, stasis or turbulent blood flow or hypercoagulability of blood = Vichow's Triad

Front 36

Venous Thrombi

Back 36

Initiated at sites of stasis

Front 37

Note thrombi in the left and right ventircular apices; they are overlying white fibrous scar tissue

Back 37

Mural Thrombi in Heart Chambers

Front 38

This is a laminated thrombus in a dilated abdominal aortic aneurysm

Back 38

Mural Thrombi in Aortic Lumen

Front 39

Back 39

Lines of Zhan
alternating pale pink bands of platelets with fibrin and red bands of red blood cells.

Front 40

Back 40

Thrombosed artery. The lumen is delineated by the internal elastic lamina (arrows). The lumen is filled with organized thrombus. The white spaces represent recanalized endothelium lined channels.

Front 41

Superficial Venous Thrombi

Back 41

Superficial venous thrombi
Generally occur in saphenous veins in the setting of varicosities
May cause local swelling, congestion, pain, and tenderness
Edema and impaired venous drainage predispose the skin to infections and varicose ulcers
Rarely embolize

Front 42

Postmortem Clots

Back 42

Gelatinous consistency with bottom portion being dark red from settling of red cells and the top portion being yellow

Front 43

Primary or secondary?

Back 43

Primary Hemostatic Defect

Front 44

Primary or secondary defect?

Back 44

Primary Defect

Front 45

Primary or secondary defect?

Back 45

Secondary; bleeding in joints

Front 46

Secondary Hemostatic Defect

Back 46

Bleeding in joints (hemarthroses) or deep tissues.
Delayed bleeding after injury.
Usually indicates clotting factor deficiency or clotting factor inhibitor.

Front 47

Primary Hemostatic Defect

Back 47

Skin or mucosal bleeding.
Bleeding immediately after injury.
Usually suggests numerical or functional abnormalities of platelets or von Willebrand disease.

Front 48

Primary or Secondary?

Back 48

Secondary; deep bleed

Front 49

Back 49

Forms platelets in BM

Front 50

Back 50

Forms platelets in BM

Front 51

Characteristics of platelets

Back 51

Cricualte for 7-10 days; removed by reticuloendothelial system third of the platelet pool is in the spleen

Front 52

Ib-IX

Back 52

Platelet receptor to adhere to endothelial surface

Front 53

IIb-IIIa

Back 53

Platelet-Platelet interaction

Front 54

Granules

Back 54

Procoagulin factors inside them; contents released when paltelets get activated

Front 55

Back 55

Pseudothrombocytopenia; platelets clot and result in low platelet count

Front 56

Any splenomegaly condition will produce what

Back 56

Thrombocytopenia due to destruction of platelets

Front 57

Back 57

B12 deficiency; folate deficiency; myelodysplasia

Front 58

Back 58

Acute leukemia; myelodysplasia; chronic leukemia

Front 59

Disseminated Intravascular Coagulation

Back 59

Excessive activation of coagulation system; thrombi formation in microcirculation; PT and PTT prolonged

Front 60

Back 60

Thrombotic thromboytopenic Purpura; deficiency of von willebrand cleaving enzyme; coaglation factors not consumed but platelet plug keeps growing so = thrombocytopeina

Front 61

Chronic Immune thrombocytopenic purpura

Back 61

Adults; detected by routine CBC; diagnosis of exclusoin, no splenomegaly

IgG Ab against paltelet glycoproteins; thrombocytopenia due to platelet removal by reticuloendothelial system

Front 62

Acute Immune thrombocytopenic purpura

Back 62

IgG Ab against paltelet glycoproteins; thrombocytopenia due to platelet removal by reticuloendothelial system

Seen in children following petechae + viral illness (chills, sore throat, etc)

Front 63

Bernard-Soulier Syndrome

Back 63

Deficiency of 1b-IX

Front 64

Glanzman's Thrombasthenia

Back 64

Deficiency of Ib-IIIa; can't form plug

Front 65

von Willebrand Factor

Back 65

Bridge between platelets and vessel wall; carrier molecule for factor VIII (so deficiency of vWF may lead to deficiency of VIII)

Front 66

Back 66

Clotting Cascade
note intrinsic vs extrinsic factor both contribute to common pathway

Front 67

Back 67

Mixing Study can tell you whether you're dealing with a factor deficiency or inhibitor

Front 68

Back 68

Palpale Purpura; immune complex deposition disease