Hemostasis and Coag Flashcards
a general term describing the process the body uses to arrest or limit the loss of blood after vascular injury
hemostasis
components of hemostasis (4)
- vascular constriction
- platelet activation (Fibrin is end product) –> coag cascade
- contraction of the platelet plug
- Clot dissolution (fibrinolysis)
extremely large bone marrow cells w/ lobulated nucleus give rise to platelets
megakaryocytes–no in circulation
pluripotential hemopoietic stem cells > megakaryoblast>
promegakaryocyte > megakaryocyte > platelets
produced by liver essential for production and right quantitiy of platelets
thrombopoietin (150-400K normal platelet count)
platelets count >600K aka and risk (2)
thrombocythemia,
stroke, DVT
platelet count <150K aka risk
thrombocytopenia,
hemorrhage
platelets express (2)
- MHC class I
2. ABO blood group antigens
(4) maintain normal circulating platelet activity
- prostacyclin (prostaglandin I2)
- nitric oxide
- endogenous heparins
- healthy endothelium
___________ _____________ molecules activate platelets
subendothelial molecules
important subendothelial molecules
- collagen
- von Willebrand factor vWF
- tissue factor
Other important factors leading to platelet activation (3)
- thromboxane A2 (TXA2)
- ADP (released by activated platelets)
- thrombin
act as bridge btwn collagen and specific platetlet surface complexes
vWF won Willebrand factor
platelet count cut-off for surgery
<50K
platelet activation steps (5)
- Exocytosis of cytoplasmic granules (ADP, serotonin, PAF, vWF, etc)
- activation of platelet membrane enzyme phospholipase A2 –> thromboxane A2
- Change in platelet shape – more amorphis
- platelet plug forms (vWF, finger-like projections, fibrinogen)
- Coagulation Cascade promoted at surface
fibrinogen promotes
activated platelets to adhere to one another
components of hemostasis (3)
- vasoconstriction
- platelet activation
- platelet aggregation and involvement of the clotting cascade which binds everything together w/ fibrin threads to form a “clot”
activation of either extrinsic or intrisic coag pathways leads to
Final Common Pathway –> fibrin formation
extrisic pathway aka
intrinsic pathway aka
- tissue factor pathway (usually more important)
- contact activation pathway
- –both involve numerous dif pts commonly called “clotting factors”
systemic inflammatory response syndrome SIRS, sepsis, and inflammation may activate the ______ ________ leading to ______
intrinsic pathway,
thrombosis
the extrinsic pathway is initiated at SITE of INJURY by
tissue factor III
intrinsic pathway activation occurs when (3) are exposed to a negatively charged surface
- prekallikerein
- kininogen
- factor XII
CONTACT ACTIVATION
intrinsic pathway activation way also occur inappropriately when contact w/ (4) correlated w/ ^ CV risk of MI due to clot formation
- bacteria
- urate crystals
- amyloid B
- homocysteine
means of controlling thrombus formation
thrombin regulation through control of prothrombin activation
thrombin inhibitors
- antithrombin III (natural inhibitor of prothrombin activation)
- Heparin
- Warfarin (Coumadin)
- Enoxaparin (Lovenox)
- Rivaroxaban (Xarelto)
- Apixaban (Eliquis)
- Dabigatran (pradaxa)
Heparin acts by
increasing effectiveness of antithrombin III – works for common pathway–IND DOSE DEPENDENT MANNER
Warfarin aka works by
coumadin–inhibits production of clotting factors II, VII, IX, and X IN DOSE DEPENDENT MANNER
Enoxaparin aka works by
Lovenox–inhibits factor Xa–FLAT DOSE RESPONSE CURVE
Rivaroxaban aka works by
Xarelto–oral–inhibits Xa–FLAT DOSE RESPONSE CURVE
aPIXaban aka works by
Eliquis–oral–inhibits Xa–FLAT DONSE RESPONSE CURVE
Dabigatran aka works by
Pradaxa–DIRECT THROMBIN INHIBITOR– FLAT DOSE RESPONSE CURVE
naturally occurring Vit K dependent anticoagulation factors
Proteins C, S, Z
ZinCS
when activated, protein C will prevent (3)
- thrombus formation
- inflammation
- blood vessel cell wall permeability
Activated (by thrombin*) protein C inactivates factors (2)
- Va
- VIIIa
localizes thrombosis to sites of vascular injury
Proteins S and Z work
in similar fashion to protein C
*Genetic defect in which factor Va is not inactivated by APC activated protein C
Factor V Leiden mutation–will lead to ^ coagulation
(2) ways to prevent thrombus formation
- Inhibit platelet function (antiplatelet) (ASA, Clopidogrel)
- Inhibit the clotting cascade (anticoag) (Hep, Warf, Vit K antagonist)
How to monitor anticoagulation over time (2)
- aPTT–Heparin–intrinsic pathway
- PT–Warfarin–extrinsic pathway
Antiplatelet Meds (6)
- Glycoprotein IIb/ IIIa inhibitors (receptor inhibitor)
- ADP receptor hinhibitor
- Prostaglandin analogue (PGI2)
- COX inhibitors
- Thromboxane inhibitors
- Phosphodiesterase inhibitors
dissolution of Fibrin Clots aka
Fibrinolysis
degradation of fibrin is a fx of ________, circulates inactive as _______
-plasmin-
plasminogen
______ ______ _____ (___) activates plasminogen
tissue plasminogen activator (tPA)
Useful measure for DVT or DIC–fibrin breakdown products
“fibrin degradation products” FDP’s and the D-dimer test–fibrin breakdown products in serum
Anticoagulation drugs (4)
- Vit K antagonists
- Factor Xq inhibitors
- Direct thrombin (II) inhibitors
- Heparin/ low mol wgt heparin
Most common uses of coagulation tests (3)
- degree of anticoag w/ drug therapy (blood thinners)
- pre-surgery (clotting problems)
- Dx inherited or acquired coag abnormality (hyper/hypo)
Blood coagulation Tests–no single lab test provides global assessment of hemostasis (7)
- platelet count
- Bleeding time
- Prothrombin time (PT)
- International Normalized Ratio (INR)
- Activated Partial Thromboplastin TIme (aPTT or PTT)
- Thrombin Time (TT)
- specific clotting factor assays
don’t confuse “clot buster” with
anticoagulant – is clot already formed?
T/F We have a good measure of the functional ability of platelets
F–only test for number of platelets
small standardized cut is made on underside of forearm and time btwn cut and complete cessation of bleeding is measured
Bleeding Time (9.5 min)–only one for vWF Dz
*Measurement of time it takes blood in test tube to form a clot–Assesses factors? – Ca++ added
Prothrombin Time (PT), factors I, II, V, VII, X (INACTIVATED)
PT tests which coag pathways
extrinsic and common pathways – clot time pt/ clot time control
INCREASED platelets disorders (4)
- acute infx
- post surg
- malignancy
- myeloproliferative Dz
INR used to asses coag in pt.’s on
warfarin
know insideout *test to assess the intrinsic (contact) and common pathways
aPTT Activated Partial Thromboplastin Time
PTT assess factors (6)
- XI
- IX
- VIII
- X
- V
- II
PTT used to assess coag in pt’s on ______
heparin
For PT (3) is added to blood tube and time to clot is measured
- tissue factor
- thromboplastin
- Ca++
Test that assesses the last step in the coag cascade
TT Thrombin Time
TT screens for (3)
- hypofibrinogenemia
- hyperfibrinogenemia
- dysfibrinogenemia (poorly functioning fibrin)
Other coag tests might look at (4)
- mixing studies
- antiphospholipid antibodies
- fibrinogen levels
- anti-factor Xa
disorders of hemostasis may be ______ or ________
inherited or acquired
most common inherited bleeding disorder
von Willebrand Dz (vWF)
tests for coag to know inside-out
- platelet count
- bleeding time
- PT
- aPTT
function of vWF
major adhesion molecule that tethers platelets to exposed subendothelium–Dz may present as along spectrum
vWF Dz types (2)
- decreased quantity of vWF
2. decreased function of vWF
vWF may present in LATER CHILDHOOD as (4)
- prolonged bleeding after surg (may be first clue)
- mucosal bleeding
- prolonged epistaxis
- menorrhagia etc
Tx for vWF Dz
DDAVP–Desmopressing–synthetic vasopressin –>release of vWF from endothelium
Hemophilia types (2) plus factor deficiency
- Hemophilia A - Factor VIII deficiency (80%)
2. Hemophilia B - Factor IX deficiency
Hemophilia etiology
X-linked recessive hemorrhagic Dz–Males clinically affected, female carriers asymp
platelet count, BT, aPTT results for hemophila
- platelet count and BT normal
2. aPTT is prolonged
Tx of hemophilia (2)
- cryoprecipitate
2. Specific Factor VIII or IX
Ashkenazic and Iraqi Jewish populations think
Factor XI deficiency (hemophilia C)
DIC
disseminated intravascular coagulation–less of Dz than syndrome
most common etiologies of DIC (3) “clot-lyse-clot-lyse-clot-lyse” –> using up all the clotting factors
- bacterial spesis (most common cx)
- malignant disorder
- obstetric complications
the exposure of blood to (4) results in uncontrolled generation of thrombin
- phospholipids from tissue damage
- hemolysis
- endothelial damage
- tissue factor
Clinical presentation of DIC (4)
- oozing from venipuncture site
- petechiae
- ecchymosis
to more extreme 4. ^ GI, pulm, CNS bleeding
most sensitive indicators of DIC
fibrin degradation products and D-dimer tests
Tx of DIC (4)
- Tx underlying cause
- replace clotting factors and platelets
- control coagulation state–heparin
- support pt–vent, dialysis, transfusion
Vit K necessary for production of factors (4) and Proteins (3)
factors II, VII, IX, X and proteins C,S,Z
Causes of Vit K deficiency (6)
- inherited deficiency
- dietary deficiency (alcoholic, starvation, food tube w/out K)
- Surgical–removal or alteration to GI tract
- Chronic ABX–colonic flora disruption
- Chronic liver Dz–primary biliary cirrhosis v Vit K
- Iatrogenic– Warfarin
Vit K characteristics
fat soluble vitamin absorbed in terminal ilium
testing for Vit K dependent clotting factors
evaluated by PT
disregulation of clotting and fibrinolysis
DIC
Tx of Vit K deficiency
- parenteral Vit K (need liver to turn into coag factors)
2. (acute) fresh frozen plasma or cryoprecipitate will replenish Vit K dependent factors
_______ often show low levels of Vit K–causes (3)
Newborns,
low transplacental transfer, low breast milk levels, sterile colon at birth
liver failure may result in ________, due to liver’s…
bleeding,
coag factors and many natural anticaog proteins
____________ common in pt’s w/ cirrhosis due to _________ _________
thrombocytopenia )
Many Endothelial:
vasodilators are-
vasoconstrictors are-
- platelet inhibitors
- platelet activators
Thrombocytopenia <150K/ul may result in
widespread petechial rash
thrombocytopenia cx (3)
- decreased production (marrow failure, infiltration, tumor)
- sequestration (spleen)
- increased destruction (over active clotting, autoimmune)
purple top tube:
Green top:
blue top:
EDTA–an aminopolycarboxylic
heparin
sodium citrate
using a “purple top” may cause
pseudothrombocytopenia–due to platelet agglutination–>falsely low platelet count
______ ___ as a metabolic by product of the colonic flora
Vitamin K–so strict dietary deficiencies are very uncommon
most common cause of non-iatrogenic thrombocytopenia
infection induced thrombocytopenia
Types/ causes of thrombocytopenia (6)
- Pseudo–purple-top
- Infection induced
- Drug induced
- Heparin induced
- Immune thrombocytopenic PURPURA (ITP)
- Thrombotic thrombocytopenic PURPURA (TTP)
Likely infection induced thrombocytopenia etiologies (3) (general category)
- Gram neg bac
- HIV
- mononucleosis EB
infection induced thrombocytopenia may result in () – generally self-limiting
- direct suppression of platelet production
- decreased survival time of platelets
- -IgG binds to platelets–>destroyed in spleen
Warfarin may induce
skin necrosis
Drug induced thrombocytopenia particularly cx by (4)
general category
- sulfonamides
- quinine
- herbal supplements
- vancomycin
mechanisms of drug induced thrombocytopenia (3)
- direct marrow suppression (i.e. chemotherapy)
- production of DRUG DEPENDENT antibodies against specific platelet surface antigens (Type II Hypersen. Rxn) upon re/exposure to drug resolves 7-10d post d/c
- cross rxn of existing antibodies w/ drug bound platlets–IMMEDIATE thrombocytopenic development
HIT (specific disease)
heparin (anticoagulant) induced thrombocytopenia
wide spread patechial rash (pinhead size red spots that don’t blanch) punctate bleeding under skin
thrombocytopenia–starts where venous pressure highest
Features of HIT (3)
- low platelet count btwn 5-14 days of starting heparin
- thrombocytopenia typically mild-moderate
3.
chloramphenicol
ABX–grey baby–destroys bone marrow–low platelets
petechiae vs purpura
smaller vs. larger–both won’t blanch
key finding in immune thrombocytopenic purpura ITP
isolated thrombocytopenia
Immune Thrombocytopenic purpura ITP in children
Fairly common in children 2-4yo–follows infectious process and generally SELF-LIMITED, resolves w/in 1-2m
presentation of immune thrombocytopenic purpura ITP pt’s (5)
- mucocutaneous bleeding
- ecchymosis (subcutaneous purpura >1 cm)
- petechiae
- epistaxis
- menorrhagia
heparin induced thrombocytopenia HIT etiology
heparin attaches to platelet–looks like foreign invader–> destroyed
in immune thrombocytopenic purpura–what might point to severe derangement which may become life threatening (2)
- wet purpura (blood blisters in mouth)
2. retinal hemorrhages
Tx for immune thrombocytopenic Purpura ITP
- mild: watch and wait
2. severe thrombocytopenia s who relapse/bleed
*Characteristics (5) of TTP aka
Thrombotic Thrombocytopenic Purpura,
- Microangiopathic hemolytic anemia
- Thrombocytopenia
- Renal Failure
- Neurologic defects
- Fever
a hemolytic anemia occurring in the microvasculature evidenced by fragmented RBC’s schistocytes, helmet cells, etc. on peripheral blood smear
Microangiopathic hemolytic anemia
microangiopathic hemolytic anemia will result in
- anemia
- increased LDH (RBC enzyme)
- increased indirect bilirubin
- decreased indirect bilirubin
- decreased haptoglobin (carries free Hgb in serum)
- increased reticulocyte count
thrombosis etiology:
arterial-
venous-
- atherosclerosis
- stasis
role of haptoglobin
carries free Hgb in serum
Tx for TTP
early recognition and prompt tx w/ plasma exchange (plasmapheresis) decreases mortality to 10-30%
plasma exchange
plasmapheresis
CNS sx of TTP
- headache
- AMS
- seizure
- stroke
Thrombosis/ thrombophilia types (3)
- arterial thrombosis
- venous thrombosis
- venous and arterial thrombosis
DX of TTP
ADAMST13 assay may be helpful + blood smear
TTP blood smear findings
- helmet cells
2. schistocytes
A disease primarly seen in children w/ 1. microangiopathic hemolytic anemia 2. acute renal failure 3. thrombocytopenia
Hemolytic uremic syndrome HUS (specific disease) very similar to TTP
differentiation for HUS and TTP
HUS: children, bloody diarrheal Dz
TTP: adults, vWF, ADAMTS13, CNS SYMPTOMS!
Thrombocytosis platelet count
> 400K
(3) cx of thrombocytosis
- Fe deficiency
- Inflammation, cancer or infxn
- Myeloproliferative process (thrombocythema or polycythemia vera)
genetic etiology of Thrombosis/ thrombophilia (3)
- ex. Factor V Leiden mutation
2. inherited deficiency of Protein C or S
Venous thrombosis–> Virchow triad (3)
- HYPERcoagulability
- Stasis or turbulent blood flow
- Endothelial injury/dysfunction
Differentiate ITP from TTP/HUC
peripheral blood smear– will not see Schistocytes/ helmet cells w/ ITP–also patient (most likely child) will be healthy and energitic w/ ITP
Venous Thrombosis RF’s
- Virchow triad
- Meds (estrogen, OCP, prothrombotics, HRT)
- obesity
- Increased age
- pregancy
Venous AND Arterial thrombosis cx’s (5)
- polycythemia versa (a bone marrow disease that leads to an abnormal increase in the number of blood cells (primarily red blood cells)) Hgb 17 viscous blood
- malignancy
- dysfibrinogenemia
- essential thrombocythemia
- TTP, DIC, and HIT
strongest predictor of recurrent venous thrombosis
idopathic thrombosis (thrombosis w/out apparent cx)
major cx of arterial thrombosis
atherosclerosis
