Clinical Lab Hemostasis
Terms
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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