15 Clotting and Coagulopathies

Question 0

GPIb alpha

Answer 0

Binds vWFand functions in initial adhesion of platelet to endothelium
Platelet activation

Question 1

GPIIb/IIIa

Answer 1

Platelette receptor for Fibrinogen, that functions in aggregation

Question 2

Dense platelette granules

Answer 2

ADP, ATP, Serotonin, CA

Question 3

Alpha granules

Answer 3

Factor-5, fibrinogen, vWF
GF- TGF-B, PDGF
Platelet factor 4

Question 4

Signaling in platelts

Answer 4

ADP, 5HT, TxA2, thrombin receptors all Gq - PLCcreates IP3 and DAG

Causes Integrin activation, granule secretion and cytoskeletal rearrangement

Question 5

Tissue Factor

Answer 5

Sub endothelial derived cofactor to VIIa, which activates 9 and 10

Question 6

VITAMIN K DEPENDANT COAGULATION FACTORS

Answer 6

2, 7, 9, 10 (allows factors to localize to membranes)

Question 7

VITAMIN K DEPENDENT ANTICOAGULANTS

Answer 7

Protein C ProteinS

Question 8

Factor 13

Answer 8

Transpeptidase connecting D termini of fibrin fibers

Question 9

tPA

Answer 9

Activators that bind and activate plasmin- which help it chew up clots.

Question 10

Thrombomodulin

Answer 10

Binds thrombin and modulates it so that it activates proteins C

Question 11

Endothelial anticoagulation

Answer 11

Release NO, and PGI2 - vaso-relaxants and inhibit platelet agregation
Heparin like molecules on surface binds antithrombin

Question 12

Antithrombin III

Answer 12

When bound to heparin like molecules inactivates Thrombin, 10a and 9a

Question 13

Mucosal bleeding

Answer 13

Suggesstive of vWF or Platelette problem

Question 14

Deep bleeding

Answer 14

Usually a factor deficiency

Question 15

Acute ITP

Answer 15

Common in children
Abrupt severe thrombocytopenia caused by autoantibodies to surface glycoproteins following an illness

Blood smear: few giant platelets, Normal reds and whites
BM: Normal to incr. megakaryocytes

Spleen important site of AB production and IgG platelette destruction.
Most children will recover spontaneously- 50% w/i 6 weeks, 90 w/i 6 months

Question 16

Chronic ITP

Answer 16

Common in adults
Insidious onset on thrombocytopenia with accumulation of bruising/ bleeding stiggmata- decreased platelet survival and production: RBC and WBC usualy normal

*Splenectomy normalizes platelets and induces remission in 2/3 of patients

Question 17

HIT

Answer 17

Heparn induced thrombocytopenia

Heparin and Platelet factor 4 complex autoantibody: IgG mediated
Get platelet activation and destruction
THROBOSIS - Arterial and Venous

Test with Elisa or serotonin release assay

Tx: Stop heparn, Treat with direct thrombin inhibitor: Argatroban Bivalirudan NEVER GIVE PLATELETS

Question 18

Thrombotic microangiopathy

Answer 18

many platelett rich thrombi in microciculation
TTP
HUS
DIC
SEPSIS

Thrombocytopenia and microangiopathich hemolytic anemia
PTT and PT usually normal

Question 19

TTP pentad

Answer 19

• Microangiopathic hemolyticc anemia*
• Thrombocytopenia**

renal failure
AMS
fever

Question 20

TTP

Answer 20

ADAMST13 deficiency, usually autoimmune- vW multimers

Schistocytosis- Treat with Plasma exchange NEVER PLATELETS
Normal coags, negative coombs

Question 21

vWF tests

Answer 21

immunoassay

Ristoccetin activation assay

Question 22

Hemolytic uremic syndrome

Answer 22

Hemolytic anemia, AKI, Thrombocytopenia

• usually kids with ecoli infection - SHIGA-likeTOXIN damages endothelials and creates platelet aggregation
• also mutation or autoantibody deficient in anticomplement protiens factor H,I, CD46

Bloody diarrhea, Renal dailure
no neurologic symptoms

TX: plasma exchange

Question 23

vW Dz

Answer 23

autosomal dominant vWF deficiency
Low vW- defect in primary coagulation with mucosal bleeding and extensive wound bleeding

Treat with Desmopressin- vWF releasing drug

Question 24

Platelete disfunction Dz

Answer 24

Bernard Soulier- GP1b deficiency | Glanzman's thromboblasthemia- GPIIb/GPIIIa

Question 25

Hemophilia A

Answer 25

Deficient in factor 8 (X-linked recessive) 30% spontaneous Can have varying activity, <1% activity is severe Massive hemorrhage after procedures or trauma Hemarthrosis Tx: Recombinante factor 8 Prolonged PTT, corrects with 1:1 mix

Question 26

Hemophilia B

Answer 26

Factor 9 deficiency x linked recessive disorder Less common than A Massive bleeding after procedures, spontaneous hemarthrosis Long PTT- normalizes with 1:1 mix Tx: Factor 9 infusion

Question 27

Vitamin K deficiency

Answer 27

Problems with Factors 2, 7, 10, 9 Cause: Warfarin, Antibiotics killing vitamin k bacteria, malabsorption/decreased intake, liver DZ, newborns TX: Plasma or cryoprecipitate

Question 28

Liver Dz coagulopathy

Answer 28

Deficient 2,7,9,10,5, antithrombin, C, S Generally balanced but low levels- balance is easily tipped Tx: Cryo, FFP, platelets

Question 29

Activated C and s inactivates what

Answer 29

8 and 5 (cofactors needed for activation of 10 and 2

Question 30

ATD, PCD, PSD

Answer 30

Antithrombin, protein C, or protein S deficiency Increaseed venous thrombosis- mostly after risk events 70% have clot by age 50

Question 31

Factor 5 leiden

Answer 31

Argenine 506, replaced with glutamine, factor 5 insucceptable to deactivation VENOUS THROMBOSIS (DDVT/PE) PTT will not slow with addition of activated C

Question 32

Prothrombin gene variation

Answer 32

elevated ThrombinII - stronger mRNA | VENOUS THROMBOSIS

Question 33

APLAS

Answer 33

Anti-phospholipid antibody syndrome - anticarrdiolipin can be positive too, along with lupis anticoagulant(prolongs dRVVT/PTT in vitro, clots in VIVO) Possible thrombocytopenia PTT prolongation that doesn't correct! and is PL dependent dilute Russell Viper Venom (dRVVT prolonged) FETAL DEMISE Venous and Arterial

Question 34

DIC Tx

Answer 34

Fix underlyying problem Bleeding: CRYO 1st!!! (need fibrinogen to fix bleeding and make clots), FFP, Platelets

Question 35

When is Fibrinogen low

Answer 35

Extensive clotting - DIC | Decreased production- Liver Dz

Question 36

When are PT, PTT, and Fibrinogen normal

Answer 36

Factor 5 leiden vW Dz Factor 13 deficiency