15 Clotting and Coagulopathies Flashcards
GPIb alpha
Binds vWFand functions in initial adhesion of platelet to endothelium
Platelet activation
GPIIb/IIIa
Platelette receptor for Fibrinogen, that functions in aggregation
Dense platelette granules
ADP, ATP, Serotonin, CA
Alpha granules
Factor-5, fibrinogen, vWF
GF- TGF-B, PDGF
Platelet factor 4
Signaling in platelts
ADP, 5HT, TxA2, thrombin receptors all Gq - PLCcreates IP3 and DAG
Causes Integrin activation, granule secretion and cytoskeletal rearrangement
Tissue Factor
Sub endothelial derived cofactor to VIIa, which activates 9 and 10
VITAMIN K DEPENDANT COAGULATION FACTORS
2, 7, 9, 10 (allows factors to localize to membranes)
VITAMIN K DEPENDENT ANTICOAGULANTS
Protein C ProteinS
Factor 13
Transpeptidase connecting D termini of fibrin fibers
tPA
Activators that bind and activate plasmin- which help it chew up clots.
Thrombomodulin
Binds thrombin and modulates it so that it activates proteins C
Endothelial anticoagulation
Release NO, and PGI2 - vaso-relaxants and inhibit platelet agregation
Heparin like molecules on surface binds antithrombin
Antithrombin III
When bound to heparin like molecules inactivates Thrombin, 10a and 9a
Mucosal bleeding
Suggesstive of vWF or Platelette problem
Deep bleeding
Usually a factor deficiency
Acute ITP
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
Chronic ITP
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
HIT
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
Thrombotic microangiopathy
many platelett rich thrombi in microciculation TTP HUS DIC SEPSIS
Thrombocytopenia and microangiopathich hemolytic anemia
PTT and PT usually normal
TTP pentad
- Microangiopathic hemolyticc anemia*
- Thrombocytopenia**
renal failure
AMS
fever
TTP
ADAMST13 deficiency, usually autoimmune- vW multimers
Schistocytosis- Treat with Plasma exchange NEVER PLATELETS
Normal coags, negative coombs
vWF tests
immunoassay
Ristoccetin activation assay
Hemolytic uremic syndrome
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
vW Dz
autosomal dominant vWF deficiency
Low vW- defect in primary coagulation with mucosal bleeding and extensive wound bleeding
Treat with Desmopressin- vWF releasing drug
Platelete disfunction Dz
Bernard Soulier- GP1b deficiency
Glanzman’s thromboblasthemia- GPIIb/GPIIIa
Hemophilia A
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
Hemophilia B
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
Vitamin K deficiency
Problems with Factors 2, 7, 10, 9
Cause: Warfarin, Antibiotics killing vitamin k bacteria, malabsorption/decreased intake, liver DZ, newborns
TX: Plasma or cryoprecipitate
Liver Dz coagulopathy
Deficient 2,7,9,10,5, antithrombin, C, S
Generally balanced but low levels- balance is easily tipped
Tx: Cryo, FFP, platelets
Activated C and s inactivates what
8 and 5 (cofactors needed for activation of 10 and 2
ATD, PCD, PSD
Antithrombin, protein C, or protein S deficiency
Increaseed venous thrombosis- mostly after risk events
70% have clot by age 50
Factor 5 leiden
Argenine 506, replaced with glutamine, factor 5 insucceptable to deactivation
VENOUS THROMBOSIS (DDVT/PE)
PTT will not slow with addition of activated C
Prothrombin gene variation
elevated ThrombinII - stronger mRNA
VENOUS THROMBOSIS
APLAS
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
DIC Tx
Fix underlyying problem
Bleeding: CRYO 1st!!! (need fibrinogen to fix bleeding and make clots), FFP, Platelets
When is Fibrinogen low
Extensive clotting - DIC
Decreased production- Liver Dz
When are PT, PTT, and Fibrinogen normal
Factor 5 leiden
vW Dz
Factor 13 deficiency
