Pathoma Chapter 4

Front 1

What is the first step of primary hemostasis?

Back 1

Transient vasoconstriction of damaged vessel

Front 2

What mediates initial vasoconstriction of vessel?

Back 2

neural stimulation and ENDOTHELIN

Front 3

Where does vWF come from?

Back 3

Platelets and endothelial cells
Weibel-Palade bodies in endothelial cells
Alpha granules of Platelets

Weibel-Palade bodies have P-selectin speedbumps and vWF

Front 4

Describe what causes platelet degranulation...

Back 4

adhesion of platelets to vWF cause shape change and subsequent degranulation with release of mediators.
ADP is released from dense granules which promotes exposure of GPIIb/IIIa receptors on platelets which is important for AGGREGATION. Also causes TXA2 to be synthesized by COX which also helps aggregation.

Front 5

Where is ADP stored in platelet?

Back 5

dense granules

Front 6

What is aggregation? how is it mediated?

Back 6

Platelet aggregation is mediated with GPIIb/IIIa receptors that were upregulated in response to ADP release from platelet dense granules
Also, Thromboxane A2, synthesized by platelet cyclooxygenase and released, which promotes aggregation.

Front 7

What is adhesion? how is it mediated?

Back 7

Platelet adhesion is mediated with vWF on basement membrane and GPIb on platelets

Front 8

What is a generally true statement about QUANTITATIVE platelet reductions as opposed to QUALITATITVE platelet reductions?

Back 8

quantitative reductions result in petechiae

Front 9

What is a bone marrow biopsy used to assess?

Back 9

Megakaryocytes, which produce platelets

Front 10

Immune Thrombocytopenia caused by...

Back 10

Antibodies binding to GPIIb/IIIa receptors on platelets. These antibodies are created in the spleen and the Ab-platelet complex is also consumed by macrophages in the spleen.

Front 11

petechiae presents in child weeks after a viral infection or immunization

Back 11

Immune Thrombocytopenia, is usually self-limited.

Antibodies bind to GPIIb/IIIa receptors on platelets

Front 12

ITP is A/W

Back 12

SLE, Lupus. Since in Systemic lupus they can have Antibodies to almost anything, RBC's, WBC's or...PLATELETS.

Front 13

Women with chronic ITP can have what complication...

Back 13

During pregnancy, since IgG can cross membrane, Infant can have transient ITP until IgG's are consumed.

Front 14

ITP lab findings

Back 14

low platelet(<50,000)
PT and PTT normal
Increase in Megakaryocytes to compensate for decrease in platelets

Front 15

One treatment for ITP is IVIG. Describe mechanism...

Back 15

When you give IVIG, you throw in so many extra platelets that your hoping the spleen will want to eat up these IgG's instead of the one's that are attached to your platelets to cause a temporary increase in platelets. This effect is SHORT lived

Front 16

Splenectomy does what in context of ITP

Back 16

eliminates the PRIMARY SOURCE of antibody AND the site of platelet destruction

Front 17

Microangiopathic Hemolytic Anemia

Back 17

Microthrombi in vessels shear RBC's into schistocytes resulting in hemolytic anemia.

Front 18

Thrombotic Thrombocytopenic Perpura is A/W what gene product?

Back 18

ADAMTS13(von Willebrand factor-cleaving protease)

Front 19

TTP Pathophys

Back 19

ADAMTS13 normally cleaves vWF multimers. ADAMTS13 is reduced in TTP and thus the multimers persist and cause abnormal platelet adhesion resulting in microthrombi.

Front 20

Common cause of TTP

Back 20

Decreased ADAMTS13(von Willebrand factor-cleaving protease) is normally due to an ACQUIRED antibody that destroys ADAMTS13, commonly seen in adult women.

Front 21

HUS A/W

Back 21

Enterotoxigenic E.Coli(O157:H7) produces verotoxin that damages endothelial cells, particularly in kidney/brain, and that creates microthrombi which shear red blood cells.

Front 22

undercooked beef, possibly in children

Back 22

ETEC O157:H7

Front 23

Most common clinical findings in HUS

Back 23

Renal insufficiency - thrombi in vessels of kidney

Front 24

Most common clinical findings in TTP

Back 24

CNS abnormalities - thrombi in vessels of CNS

Front 25

Lab findings in TTP/HUS

Back 25

Thrombocytopenia with INCREASED bleed time
NORMAL PT/PTT
Anemia with Schistocytes
Increased megakaryoctes as a compensatory response(hyperplasia)

Front 26

Bernard-Soulier syndrome

Back 26

genetic GPIB deficiency; platelet ADHESION impaired

blood smear shows thrombocytopenia with enlarged platelets.
enlarged because they are slightly more immature

Front 27

Glanzmann's Thrombasthenia

Back 27

genetic GPIIB/IIIA deficiency; platelet AGGREGATION is impaired

Front 28

Aspirin MOA

Back 28

blocks COX irreversibly. Blocks production of TXA2 which impairs AGGREGATION. Important chemoattractant for other platelets.

Front 29

Uremia. How does it affect clot formation?

Back 29

Uremia is a buildup of nitrogenous waste products due to poor kidney function - both adhesion and aggregation are impaired

Front 30

what happens when fibrin is cross linked?

Back 30

stable clot formed...

Front 31

What three things are required to activate factors of coagulation cascade?

Back 31

1.) Phospholipid surface - provided by platelets

2.) Activating substance - Tissue thromboplastin/Tissue Factor activates Factor VII or Subendothelial collagen activates factor XII.

3.) Calcium

Front 32

defective Secondary hemostasis clinical symptoms

Back 32

deep bleeding, rebleeding

Front 33

PT

Back 33

extrinsic

Front 34

PTT

Back 34

intrinsic

Front 35

Hemophilia A
genetic inheritance?

Back 35

Hemophilia EIGHT
X-linked recessive
Factor VIII deficiency
New mutation common

Front 36

describe a Mixing study and what it's used for

Back 36

Mixing study used to distinguish between Hemophilia A and Coagulation Factor Inhibitor(antibody against Coagualation Factor)

Normal Plasma + Patient Plasma will yield normal bleed time if Hemophilia A. If CFI, then circulating Ab blocks factor VIII again(party pooper)

Front 37

Most common inherited coagulation disorder

Back 37

Genetic deficiency of vWF

Front 38

what secondary quality does vWF have? Relevance?

Back 38

stabilizes factor VIII. As such, in vWF deficiencies, PTT goes up.

Front 39

Ristocetin

Back 39

Ristocetin causes platelets to bind to vWF via their GPIb receptor.

A test is abnormal in a vWF deficiency since the platelets cannot bind, which causes lack of adhesion/aggregation

Front 40

Desmopressin

Back 40

increases release of vWF from Weibel Palade bodies in endothelial cells.

Front 41

what is the physiological function of Vitamin K?

Back 41

allows gamma-carboxylation of 2,7,9,10, Protein C and Protein S.

Front 42

MOA of Warfarin/Coumadin

Back 42

Blocks epoxide reductase in liver, which activates vitamin K which then gamma carboxylates the necessary coagulation factors(2,7,9,10,C,S) to allow their normal function.

If epoxide reductase blocked, vitamin K cannot be activated and PT goes up.

Front 43

How do you follow liver function?

Back 43

Check PT

Front 44

Large volume transfusion?

Back 44

Causes a relative dilution of coagulation factors

Front 45

How does liver function affect coagulation cascade?

Back 45

--Liver synthesizes most of the coagulation factors.
--It is also the main site of epoxide reductase, which activates vitamin K.

If your liver fails, then not only can you not MAKE the factors, but you can't activate Vit K to make the factors functional via Vit K dependent gamma carboxylation.

Front 46

Fat malabsorption

Back 46

Bad for vitamin absorption, particularly fat soluble ones

Vitamins D, A, K, E

Front 47

Dense core granules of platelets contain?

Back 47

ATP, calcium and serotonin

Front 48

alpha granules of platelets contain?

Back 48

everything else except calcium, serotonin and ATP

vWF, fibrinogen, coagulation factors V and XIII, fibronectin, platelet factor 4

Front 49

Most common coagulation factor inhibitor?

Back 49

Factor VIII

Front 50

What complication do you give vitamin K to newborns to prevent?

Back 50

hemorrhagic disease of the newborn

Front 51

Heparin induced thrombocytopenia

Back 51

Heparin causes a decrease in platelet count because of the formation of a complex with platelet factor 4

IgG antibodies against platelet-heparin complex that the spleen proceeds to destroy

Front 52

Platelet factor 4 stored in what granule in platelet?

Back 52

alpha granule

Front 53

Cause of DIC in pregnancy

Back 53

TF(thromboplastin) in amniotic fluid activates coagulation

Front 54

Acute Promyelocytic Leukemia

Back 54

Contain auer rods which can enter circulation and cause DIC

Front 55

Rattlesnake bite

Back 55

venom enters circulation causing DIC

Front 56

Lab findings of DIC

Back 56

decreased platelets
increased PT/PTT
decreased fibrinogen
Microangiopathic Hemolytic Anemia(Schistocytes)
Elevated fibrin split products(D-dimer)

D-dimer is an indicator of lysed cross-linked fibrin. Elevated D-dimer is the BEST test for DIC.

Front 57

What hallmark lab finding is found in DIC?

Back 57

elevated D-dimer

Front 58

tPA

Back 58

converts plasminogen to plasmin

plasmin cleaves cross-linked fibrin(clot), fibrinogen(ability to form new clots), destroys coagulation factors, and blocks platelet aggregation

produced by endothelial cells

Front 59

What inactivates plasmin?

Where is this protein produced?

Back 59

alpha-2-antiplasmin.

Liver

Front 60

What diseases are a/w overactivity of plasmin

Back 60

radical prostatectomy - release of urokinase activates plasmin

liver cirrhosis - reduced production of alpha-2-antiplasmin

Front 61

Lab findings of disordered fibrinolysis. What lab value is normal?

Back 61

-- increased PT/PTT
-- increased bleeding time--since plasmin blocks platelet aggregation
-- increased fibrinogen split products WITHOUT D-dimers.
-- NORMAL platelet count

Front 62

blocks activation of plasminogen

Back 62

aminocaproic acid

Front 63

Features distinguishing from post-mortem clot

Back 63

1.) Lines of Zahn
2.) attachment to vessel wall

Front 64

Thromboxane A2

Back 64

it stimulates activation of new platelets as well as increases platelet aggregation

produced by platelets

Front 65

Prostoglandin I2

Back 65

protects against thrombosis, blocks platelet aggregation

produced by endothelial cells

Front 66

Heparin like molecules

Back 66

augments anti-thrombin III which inactivates thrombin and coagulation factors(notably factor Xa)

produced by endothelial cells

Front 67

thrombomodulin

Back 67

Modulates activity of thrombin. Thrombomodulin redirects activity of thrombin from activating fibrinogen to fibrin towards activating Protein S to Protein C which proceeds to inactivate factors V and VIII

Front 68

increase of homocysteine does what?

Back 68

damages endothelium. This can be caused by Vitamin B12 deficiency OR a folate deficiency(THF)

can also be caused by Cystathione Beta Synthase deficiency which leads to vessel thrombosis, mental retardation, lens dislocation and long slender fingers.

Front 69

What causes high levels of homocysteine?

Back 69

Vitamin B12 or folate deficiency
or
Cystathionine Beta Synthase(CBS)
CBS converts homocysteine to cystathione; enzyme deficiency leads to buildup of homocysteine

Front 70

Vessel thrombosis, mental retardation, lens dislocation and long slender fingers(arachnodactyly)

Back 70

Cystathionine Beta Synthase clinical symptoms

high serum homocysteine causes vessel thrombosis.

Front 71

recurrent DVT's in children

Back 71

hypercoagulable state

Front 72

Protein C and S deficiency a/w

Back 72

Warfarin/Coumadin skin necrosis

MOA
Warfarin blocks epoxide reductase in liver which activates Vitamin K.
No vitamin K disables 2,7,9,10, protein C and protein C.

Protein C and S are first to degrade with loss of Vitamin K, therefore these anti-coagulants are lost first while the coagulation factors 2,7,9,10 are still around leading to a relative hypercoagulable state. As such, these patients are simultaneously given heparin to reduce temporary levels of 2,7,9,10.

Front 73

Factor V Leiden

Back 73

Most common hypercoagulable state

mutated factor V that is resistant to
Protein C and Protein S cleavage.

Front 74

Prothrombin 20210A

Back 74

hypercoagulable

mutation that leads to increased levels of prothrombin and thus levels of thrombin.

Front 75

ATIII Deficiency

Back 75

ATIII when activated, normally inactivates thrombin and factor Xa

ATIII deficiency means that heparin-like molecules secreted by endothelial cells are useless.
NOTABLY this renders heparin completely fucking useless, since the MOA of heparin works via ATIII. As such, PTT does NOT rise in response to standard Heparin treatment.

Front 76

MOA heparin

Back 76

activates ATIII which inactivates thrombin and factor Xa.

Front 77

Why are oral contraceptives associated with hypercoagulable state?

Back 77

Estrogen increases production of coagulation factors

Front 78

What is characteristic of atherosclerotic embolus?

Back 78

cholesterol clefts in the embolus

Front 79

risk after fracture of bone shortly after repair

Back 79

fat embolus

Front 80

who is at risk for Gas embolus

Back 80

Divers and laparoscopic surgery

Front 81

Caisson disease. What disease will this cause?

Back 81

Characterized by multifocal ischemic necrosis of bone

due to gas embolus

Front 82

What notable and relevant substance is in amniotic fluid?

Back 82

Tissue Factor/Thromboplastin

causes DIC if it enters maternal circulation

Front 83

Amniotic fluid embolus clinical symptoms

Back 83

Shortness of breath, neurologic symptoms and DIC

Front 84

What notable lab finding is present in PE?

Back 84

D-dimer elevated because of the cleavage of the fibrin in DVT as well as PE.