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81 Cards in this Set
- Front
- Back
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4 mechanisms for thrombocytopenia
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decreased production
increased destruction increased consumption increased sequestration in spleen |
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thrombosis
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stagnation of blood flow as a result of arterial disease or mechanical impedence. Leads to thrombus clots/hypercoagulable states
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Primary hemostasis
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Platelet adhesion to exposed collagen (primary platelet plug) and vasoconstriction; fragile and easily disolodged
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platelet adhesion is mediated by...
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adherence of vWF that binds to glycoprotein Ib receptors on the platelet
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Clinical symptoms of thrombocytopoenia
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petechiae, hemorrhage, prolonged bleeding time, impaired clot retraction
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Megakaryocyte disorders are classified as
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Congenital (fanconi's anemia, maternal infection)
Acquired (radiation, alcohol, cancer chemotherapy) Marrow dysfunction (leukemia, lymphoma, etc.) |
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megaloblastic anemia will do what to platelets
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cause thrombocytopenia due to ineffective production of platelets
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Hypothermia willl cause thrombocytopenia. why?
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Vascular shunting to internal organs
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Why does promyelocytic leukemia cause an increase in consumption of platelets?
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Platelets will adhere to promyelocytes
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bacterial and viral infections will cause a _________ (re platelets)
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increased destruction of platelets
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define thrombocytopenia and thrombocytosis
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penia: <140e9 plts/L
cytosis: >450e9 plts/L |
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Thrombocytopenia will do what to bleeding time?
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Increase it as count drops below 100e9/L
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Primary thrombocytosis is caused by
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- primary bone marrow disorder
- clonal proliferation that affects all hematopoietic cells (hodgkin's, polycythemia vera, myelofibrosis, chronic myelogenous leukemia, thrombocythemia) |
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secondary thrombocytosis is caused by...
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IDA (chronic blood loss) chronic inflammatory disease, splenectomy, rebound thrombocytosis (following massive blood loss)
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ITP
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idiopathic (immune) thrombocytopenic purpura
- autoimmune disorder - inc mean platelet volume - low plt count - platelet associated IgG |
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acute ITP is most common in which age group and is associated with what other diseases?
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children 2 - 6 years old
associated with viral infections: rubella varicella cytomegalovirus toxoplasmosis |
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Pathophysiology of ITP
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viral attachment and antigenic alteration of platelet membrane proteins; this results in formation of platelet autoantibodies
IgG coated platelets are removed by macrophages in the spleen |
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Treatment of choice for ITP
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corticosteroids; suppress macrophages, decreased Fc receptor function; decreased antibody-platelet binding
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chronic ITP is most commonly found in which demographic?
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women of childbearing age (20-40 yo)
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Characteristics of chronic ITP
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slow asymptomatic onset of thrombocytopenia that lasts months to years
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treatment of ITP
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splenectomy and corticosteroids
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chronic ITP is associated with which which disorder?
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systemic lupus erthomatosus
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TTP
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thrombotic thrombocytopenic purpura
- caused by excessive deposition of platelet aggregates in renal and cerebal vessels - caused by vascular wall dysfunction (inert basement membrane) |
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TTP demographic and clinical symptoms
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More common in men 30-40 years old
- microangiopathic hemolytic anemia - thrombocytopenia - headache/seizure - fever - renal disease |
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PT, APTT and fibrinogen for TTP are...
FDP (fibrin degredation products) for TTP |
commonly (>88%) normal (not an issue with secondary hemostasis)
due to vascular endothelial damage, FDP will be positive/weak positive a little under 50% of the time |
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Inherited megakaryocytic hypoplasia is considered when...
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Thrombocytopenic patients with no platelet antibodies
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acquired megakaryocytic hypolasia is associated with
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alcohol toxicity, viral infection and congenital states
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nonimmunologic platelet loss or destruction
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sever hemorrhage, extensive transfusion or IV (dilution) and consumption
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hemolytic uremic sydrome effects on platelet count
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intraglomelular thrombi formation causing renal dysfunction, proteinuria and hematuria
- anemia/thrombocytopenia is milder than in TTP |
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HUS is commonly seen in which cases
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Children with hemorrhagic E. coli infection
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HUS laboratory symptoms
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BUN, creatinine, proteinure, hematuria increased
PT, APTT, D-dimers, FDP normal Burr cells are PRESENT in HUS but not TTP/DIC |
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DIC
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disseminated intravascular coagulation
- occurs in all age groups - commonly secondary to infections and leukemias |
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LD/bilirubin/haptoglobin is ____ in DIC/TTP/HUS
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increased; indirect; decreased
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difference of HUS/TTP from DIC
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PT, APTT will be increased in DIC
FDP and D-Dimers will be + in DIC |
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Lab findings for bernard soulier disease:
platelet ct and morphology bleeding time clot retraction PF3 platelet adhesion |
mild to moderate thrombocytopenia
"giant platelet disease" 2.5-8um BT > 20 min normal clot retraction normal PF3 activity decreased platelet adhesion |
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Glanzmann's thrombasthenia general characteristics
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autosomal recessive gene
both sexes affected equally homozygocity required for disorder more common among middle eastern/south asian populations |
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Glanzmann's thrombasthenia pathophysiology
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defect in GP IIb/IIIa complex
Problem with fibrinogen being unable to bind to GP IIb/IIIa |
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Glanzmann's thrombasthenia clinical presentations
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brusing, epistaxis, mucous hemorrhage, GI hemorrhage, menorrhagia
ecchymoses severity decreases with age transfusion may be required |
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Glanzmann's thrombasthenia lab findings:
platelet ct clot retraction PF3 availability BT ADP, epinepherine, collagen, thrombin and ristocetin |
normal platelet ct
normal clot retraction PF3 availability decreased prolonged BT abnormal adhesion Platelet aggregation no ADP, epinepherine, collagen or thrombin Normal ristocetin |
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What is a hypercoagulable state?
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Recurrent thrombosis due to either hereditary or acquired hypercoagulable risk factors
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Pathophysiology of hypercoagulable states
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Excessive clotting in combination with vascular inflammation + endothelial injury, dec. blood flow, or procoagulant/anticoagulant imbalance
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Mean age at first thrombosis for inherited hypercoagulable states
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35-40 yr
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What suggests an acquired hypercoagulable state?
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If a person has a thrombosis after having pregnancy or surgery without thrombotic complication
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What suggests an inherited hypercoagulable state?
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documented venous thromboembolism before 50 yr in a first degree relative
or spontaneous idiopathic thrombosis, esp. in younger individuals |
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What are high risk factors for thrombosis?
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Antithrombin deficiency, protein C deficiency, protein S deficiency
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What are modest risk factors for thrombosis?
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Factor V Leiden
Prothrombin mutation 20210A Hyperhomocysteinemia Oral contraceptive use |
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What syndrome is closely associated with acquired hypercoagulable states?
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Antiphospholipid antibody syndrome
other stimuli: age, oral contraceptives, pregnancy, surgery, trauma |
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Venous thrombosis is associated with
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Resistance to protein C/factor V leiden
prothrombin mutation 20210A Antithrombin deficiency Protein C deficiency Protein S deficiency |
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Arterial thrombosis is associated with
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antibodies associated with heparin-induced thrombocytpenia
chronic DIC lipoprotein A |
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Pathogenic thrombosis occurs when
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a clot is extended beyond its beneficial size
a clot occurs inappropriately at sites of vascular disease A clot embolizes to other sites in circulation Actions of fibrinolytic systems fail to occur |
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Protein S (by itself) clan inhibit which factors
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VIIIa, Xa and Va
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activated protein C in cojunction with ____ can inhibit which factors
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Protein S; factor Va and VIIIa
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EPCR
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endothelial cell protein C; a receptor that binds ProC and aProC and inactivates it;
levels increase in DIC and SLE (lupus) |
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Protein S is dependent on which vitamin
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K
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What induces Protein S secretion and where is it synthesized?
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Induced by IL-4 in T cells; synthesied by megakaryocytes and kidneys
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aProC levels are determined by
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levels of ProC
thrombin generation thrombomodulin and EPCR availability Plasma alpha-1 antitrypsin Alpha-2 macroglobulin |
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What is the most important inhibitor of clotting factor proteases?
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Antithrombin IIII (ATIII)
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Differentiate Type I and type II ATIII deficiency
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Type I: decreased conc,, decreased functionality when combined with heparin
Type II: molecular defect, normal concentrations but not deficient |
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Factor V Leiden
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mutation of Factor Va that is resistant to anticoagulant activity of aProC
- alters steric site for binding aPC - seen in 10-30% of pt's with DVT |
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What are some causes of thrombocytosis
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Essential thrombocythemia
Myeloproliferative disorder Myelodysplastic syndrome Reactive Thrombocytosis (blood loss, IDA, postsplenectomy, rebound, inflammation) |
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What are the laboratory results for essential thrombocythemia?
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-lack of philadelphia chromosome
-collagen fibrosis of marrow -increased platelets with normal H&H -v. high plt count (>600k/uL) |
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Patients with essential thrombocythemia are likely to convert to acute anemia (T/F)
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False; they are not likely to develop leukemia
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What is the preferred treatment for essential thrombocythemia and why?
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aspirin;
- prevents thrombus formation - low doses will prevent bleeding episodes |
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Afibrinogenemia
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An inherited as an autosomal recessive trait.
Bleeding disorders: gum bleeding, epistaxis, menorrhagia, GI hemorrhage, muscle hemorrhage, spontaneous aboritons |
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Fibrinogen concentration for normal adult
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150-350 mg/dL
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Lab findings for afibrinogenemia
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prolonged PT, APTT and thrombin time
Increased bleeding time Abnormal platelet aggregation |
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Dysfibrinogeneia
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Fibrinogen molecular defect, impaired release of fibrinopeptides, defects in fibrin polymerization and crosslinking
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Treatment for afibrinogenemia
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Plasma or conc. fibrinogen infusion for life
cryopercipitate |
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What do FDP's do?
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Have a anticoagulant effect by inhibiting fibrin polymerization, as well as competitive inhibition of thrombin
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Thrombin time infinitely prolonged, reptilase time infinitely prolonged
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Dysfibrinogenemia or afibrinogenemia
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Prolonged thrombin and reptilase time
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Hypofibrinogenemia
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Prolonged thrombin time and normal reptilase time
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Heparin
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Prolonged thrombin time and slightly to moderately prolonged reptilase time
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FDP
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Purpose of mixing studies
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Used to assess the cause of prolonged coag screens (PT/APTT)
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PNP
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pooled normal plasma: plasma that contains all coagulation factors in their functional assay form (100% activity)
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How is the efficacy of coagulation factors measured
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in percent activity (not time like PT/APTT)
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Correction vs. no correction
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Correction: factor deficiency
No correction: circulating inhibitor has acted upon both the patient plasma and the biologically active factors in PNP |
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Factor VIII is time and temperature (dependent/independent)
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dependent for both
- will not show correction following 2 hr incubation at 37C |
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Absorbed plasma contains factors...
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I, V, VIII, XI, XII and XIII
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Aged serum contains factors...
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VII, IX, X, XI, and XII
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Case:
PT: normal APTT: prolonged APTT post-aged serum: 87 s APTT post-absorbed plasma: 50 s |
Factor VIII deficiency
normal PT: not factor I, V, VII and X post-AS NC: not factors IX, X and XII post-AP C: VIII |
