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Clinical Lab Hemostasis

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What are the four major systems involved in maintaining hemostasis?
vascular system
platelets
Coagulation
Fibrinolysis
What does bleeding from arterioles and venules produce?
petechiae
what does bleeding from veins produce?
ecchymosis
How does the vascular system maintain hemostasis?
Prevents bleeding by vasoconstriction, diversoin of blood away from damaged area, contact activation of platelets, activation of coag system
How dod platelets maintain hemostasis?
The have dense granules of ADP, attract other platelets to site of injury and form platelet plug. Activation of PF3 facilitates thrombin formation by int. coag system
What does aspirin do?
Inhibits cyclooxygenase, which blocks the formation of prostaglandins, thus preventing platelet aggregation
Where are Coag factors produced?
All produced in liver, except for factor VIII, which is produced by platelets
What stabilizes the platelet plug?
Fibrinogen (factor I), it is the end stage of both the int and ext coag cascades
What 2 factors cannot be quantified?
III (tissue factor/ thromboplastin)
XIII (fibrin-stabilizing factor)
What type of factors does the PT test?
Extrinsic factors, vit K dependent
I, II, V, VII, X
What is the antidote for excessive warfarin therapy?
vitamin K
What tube is PT drawn in?
What is ratio?
blue tube with Na citrate
ration should be 4.5/.5
What may prolong the PT?
Alcohol, diarrhea, malabsorption, ASa, allopurinol
What may shorten PT?
diet high in fat or green leafy vegetables, benadryl, ocp's
Who is on Warfarin therapy?
Contraindicated?
pts s/p hip/knee replacements, afib, PE, DVT, TIAs
Contraind in pregnancy, use heparin
What's the INR
International Normalized Ratio - standardizes PT results
Normal ther. range of INR
For mech heart valve
2-3
3-4.5
What is PTT?
Partial thromboplastin time
measures intrinsic coag system: 1,2,5,8,9,10,11,12
When is PTT used?
To measure heparin therapy
What does heparin do?
inactivates prothrombin (2) and prevents formation of thromboplastin
When should PTT be drawn when monitering heparin therapy?
30-60 minutes before next dose
How can hep effects be reversed?
protamine sulfate
What is normal PTT?
30-45 secs
What is APTT
more sensitive version of PTT, activators are added to reagents. NOrmal is 21-35 secs
What is Bleeding Time an indicator of?
platelet function
What is heparin?
high molecular wt compound taht is an anti-thrombin III antagonist. It accelerates the binding of antithrombin III to thrombin.
What is in vivo half life of heparin?
90 minutes
When is FSP increased?
What is replacing it?
DIC, DVT, MI, PE, hepatic dysfunction
Replased by D-dimer
How are d-dimer fragments produced?
Fibrin acted on by plasmin
When do you see decreased levels of fibrinogen (I)
malnourished, liver disease, comsumptive coagulopathies, large volume transfusions
What meds change levels of fibrinogen?
increase:estrogen, OCP
decrease: depakote, androgens, dilantin
Thrombin Time
Normal 10-14 secs
Thrombin acts on fibrinogen conversion to fibrin
aids in eval of long ptt
detects presence of hep, decreased fibrinogen
Congenital anti-thrombin III deficiency results in?
disorder that predisposes patient to thrombosis
Hypercoagulable states are associated with?
malignancy (Trousseau’s syndrome), pregnancy, nephritic syndrome, OCPs, pure estrogen, ulcerative colitis, Crohn's, intravascular devices
Gen characteristics of bleeding disorders
excessive or repetitive bleeding or bleeding at unusual sites
may be congenital or acquired
Congenital bleeding disorders involve defects related to?
vascular integrity,plt function, coagulation or fibrinolytic systems
Acquired bleeding disorders usually involve?
more than one system-eg. kidneys, collagen vascular, immune system-may be drug-induced, secondary to neoplasm, malabsorption, or OB complications
What lab tests are done to look for bleeding disorders?
CBC with diff, plt count, bleeding time,pt,ptt,thrombin time
Thrombocytopenia
dec. plts, may be 2dary to impaired production, inc destruction, sequestration or dilution
What med should be avoided in thrombocytopenia, why?
Aspirin, becauses is is a platelet antagonist
Idiopathic thrombocytopenia purpura - acute, found most common in?
Children, associated with preceding URI
signs and symps of ITP, acute
acute onset of petechiae and purpura on skin and mucus membranes
Labs: dec plts, eosinophilia, mild leukocytosis
prognosis and tmt of acute ITP
usually resolves spontaneously, may require corticosteroids or splenectomy
Chronic ITP - who gets it?
occurs at any age, women are more common, other autoimmune diseases common often present
signs and symps of chronic ITP
usually asymptomatic, may have petechiae
Labs: low plt count, but not as low as acute
Tmt of chronic ITP
corticosteroids, IV gamma globulin, immunosuppressive agents, occasionally splenectomy
DIC
Desseminated Intrinsic Coagulopathy, type of plt cons syndrome
Plt consumption syndromes, what happens?
widespread deposit of thrombi in the microcirculation of all organs
How is DIC initiated?
tissue thromboplastin stimulates extrinsic cascade, sources of tp: hemolyzed rbcs, placental, neoplastic and traumitized tissue
Labs in DIC
prolonged pt, ptt, thrombin time, increased FDP, decreased plts and fibrinogen, schistocytes seen on peripheral smear, elevated d-dimer, prolonged clot retraction
What drugs cause increased fibrinogen?
estrogen, bcp
What drugs cause decreased fibrinogen?
depakote, androgens, dilantin
What does thrombin do?
Thrombin acts on fibrinogen conversion to fibrin.
Normal thrombin time
10 -14 secs
When is thrombin time used?
Used to detect presence of heparin, decreased fibrinogen, aids in evaluation of prolonged PTT.
Congenital antithrombin III deficiency results in?
disorder that predisposes pt to thrombosis
Protein S and Protein K
Vit K dependent factors important in anticoagulation
General characteristics of bleeding disorders
involves excessive or repetitive bleeding or bleeding at unusual sites
may be congenital or acquired
Congenital bleeding disorders are related to defects in?
vascular integrity, platelet function, coagulation, or fibrinolytic systems.
Lab test for bleeding disorders
cbc with diff, plt count, bleeding time, pt, ptt, thrombin time
Why should asa be avoided in thrombocytopenia?
its is a plt antagonist
Acute Idiopathic thrombocytopenia purpura, who gets it?
usually children, after viral URI
acute ITP, signs and symps
acute onset of petechiae and purpura on skin and mucus membranes
acute ITP labs
decreased platelets (10-20,000), eosinophilia, mild leukocytosis
acute ITP tmt
usually resolves spontaneously, may require corticosteroids or splenectomy
Chronic ITP, who gets it?
may occur at any age, is more common in women, other autoimmune diseases are often present
Chronic ITP, signs and symps
patients are generally asymptomatic, may have petechiae
Labs for chronic ITP
platelet count is low at 25-75,000
Platelet consumption syndromes
widespread deposition of thrombi in microcirculation of all organs
Key symptom of DIC
BLEEDING
Effects of DIC
prolonged PT, PTT, and Thrombin times, increased FDP, decreased platelets and fibrinogen, schistocytes seen on peripheral smear, elevated D-dimers, prolonged clot retraction
tmt of DIC
treat underlying cause
FFP, cryoprecipitate
Thrombotic thromobocytopenia purpura, who gets it?
Rare, can be fatal, seen in women who are previously healthy
Signs and symps of ttp?
severe thrombocytopenia with purpura, hemolytic anemia, fever, abnormal neurological signs, and renal dysfunction. Negative Coomb’s.
tmt of ttp
corticosteroids, plasmapherisis, ffp
Hemolytic Uremic Syndrome
often found in children. Identical to ttp, but only in kidney. Same tmt as ttp, better prognosis
Ass. w/ E.Coli 0157:H7
HELLP
Hemolysis, Elevated Liver enzymes, Low Platelets
Signs and symps of HELLP
Pregnancy: htn, proteinuria, renal dysfunction (preeclampsia) to cerebral edema and seizures (eclampsia)
? cause of HELLP
abnormal prostaglandin metabolism
How is HELLP reversed
Delivery
Most common cause of acquired plt dysfunction
asa and NSAID use
hemophilia A, aka
who gets it?
Factor VIII deficiency, classic hemophilia
hereditary, x-linked rec.
signs and symps
mild to severe, post surg/trauma bleeding, hemarthroses, epistaxis, intracranial bleeds, hematemesis, melena, gingival bleeds
Lab studies for hemophilia A
prolonged ptt, normal pt, normal bleeding time, normal plt. Factor VIII and VIIIc activity are reduced, while factor VIII antigen is normal
Tmt for hemophilia A
ffp, cryoprecipitate given pre surgery, precedures.
desmopressin DDAVP may elevate factor VIII levels
Hemophilia B
Factor IX deficiency, aka christmas disease
similar to A but less frequent
VonWillebrand's Disease
Who gets it?
Congenital, autosomal dominant, equall affects men or women, occurs in 6 major types
VonWillebrand's
signs and symps
Nasal, sinus, vaginal, and GI mucus membrane bleeds, spontaneous hemarthroses and soft tissue bleeds are less common
VonWillebrand's, Lab studies
prolonged bleeding times and decreased levels of factor VIII
VonWillebrand's Tmt
FFP, cryoprecipitate, or desmopressin.
Vitamin K deficiencies
General
Most common acquired coagulopathy. May be due to malnutrition, malabsorption, drugs
Vit K deficiencies - Labs
PT/PTT are prolonged, normal bleeding time, liver enzymes may be elevated, levels of vitamin K and factors II, VII, IX, and X are decreased
Tmt of Vit K deficiencies
vitamin K restores factor production, hemorrhage is treated with FFP

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