What does vWF bind to on the platelets?
Damanged endothelium-->circulating vWF in plasma attaches to endothelium, platelets attach to vWF using GPIb/V/IX
Platelets have alpha granules and delta (dense) granules. What do they contain?
*hint* dense only have 4 things whereas alpha has a lot so easiest to memorize contents of dense granule
-ADP dense granule which causes vasoconstriction
- platelet fibrinogen
After vWF attaches to endothelium and platelets, platelets release their granules and change shape with expose their fibrinogen receptors. What receptor binds fibrinogen? What drugs inhibit this receptor?
GPIIbIIIa inhibitors: Abciximab-Reopro, Integrilin,
Where is vWF made (two sites)?
Endothelial cells (Weibel-Palade bodies) and megakaryocytes (alpha granules)
Coagulation cascade is divided into intrinsic and extrinsic pathways based on in vitro methods. What activates these pathways?
•Intrinsic path activated by blood in contact with negative charged glass
•Extrinsic path activated by tissue factor (subendothelium)
What are the steps of fibrinolysis (breaking down clot)?
Tissue plasminogen activator (TPA) cleaves plasminogen to plasmin
Plasmin cleaves fibrin into fibrin split products
What are the there inhibitors of fibrinolysis?
1. Alpha two antiplasmin inhibits plasmin
2. PAI inhibits plasminogen
3. TAFI (thrombin activatable fibrinolysis inhibitor)
inhibits binding of plasminogen and TPA to fibrin
How does protein C function?
Thrombomodulin binds to thrombin to activate protein C; with its carrier, protein S, activated protein C inhibits FV and FVIII
How does antithrombin function?
Liver-produced AT binds to heparin and inhibits conversion of II to IIa; also inhibits Xa action
Technically, how does the PTT test work?
– Take negatively charged surface phospholipid (partial thromboplastin)
– Add PPP + calcium chloride
– Measure the time to clot
• Normally < 40 seconds
• Measures intrinsic & common pathway
• Measures all factors except 7 and 13
Technically, how does the PT test work?
– Take tissue factor and phospholipids
– Add citrated patient’s platelet-poor plasma (PPP) & calcium chloride
– Measure the time to clot
• Normally < 15 seconds
• Measures the extrinsic and common pathways
Technically, how does the thrombin time work?
– Take exogenous thrombin
– Add PPP
– Measure time to clot
• Measures common pathway
• Measures conversion of fibrinogen to fibrin
• Doesn’t need Ca or phospholipid
• increased paraprotein, amyloid, heparin, dysfibrinogenemia
Technically, how does the reptilase time work?
– Take Bothrops atrox venom
– Add PPP
– Measure time to clot
• increased reptilase time in dysfibrinogenemia
• If patient is on heparin, they will have an increased TT but nl reptilase time
• Reptilase measures conversion of fibrinogen to fibrin, but is
insensitive to heparin
• heparinase + protamine will correct TT that is increased in a patient on heparin
Which factor inhibitor will correct with an immediate mixing study but then prolongs after 1-2 hours (time dependent prolongation)?
Factor VIII inhibitor
What happens in mixing studies with:
1) Partially corrects
2) Completely corrects
What disorder is characterized by a defect in GPIb/V/IX (CD42), shows LARGE platelets with pseudonucleolus, has impaired ristocetin aggregation?
What does Bernard Soulier show on flow cytometry?
Decreased CD42a, CD42b and CD42d
(which corresponds to GPIb, V, and IX)
What disorder is characterized by a platelet aggregation problem because platelets can't bind fibrinogen and this is from abnormal GP IIb-IIIa receptor?
What platelet disorder shows impaired ristocetin aggregation on PFA?
What platelet disorder shows impaired aggregation with ADP, collagen and epinephrine but NORMAL ristocetin?
What are the flow cytometry findings in Glanzmann thrombasthenia?
Decreased CD41 and CD61
(corresponds to GPIIb and GPIIIa respectively)
What is the main differential with Glanzmann thrombasthenia and how do you tell them apart?
Glanzmann and Afibrinogenemia
*Glanzmann's has normal PT and PTT
Afibrinoginemia has increased PT and PTT
What disorder is has giant platelets AND WBC inclusion, is autosomal dominant mutation in myosin heavy chain 9 gene, has thrombocytopenia but very little bleeding and normal PMN function?
May Hegglin Anomaly
What is the mutation in May Hegglin anomaly?
Myosin heavy chain 9 gene
What disorders can cause giant platelets?
• ITP, May Hegglin, gray platelet syndrome, Bernard Soulier, Montreal plt syndrome, DiGeorge syndrome
• Mediterranean macrothromocytosis
• Sebastian, Fechner, Epstein, and Alport syndromes
What platelet disorder is characterized by decreased platelet aggregation due to deficiencies in either dense granules/alpha granules or both?
Storage Pool Deficiency
normal morphology, no granules on EM
This platelet aggregation suggests what disorder?
Storage Pool Deficiency
NO 2nd wave wtih ADP and Epinephrine
DECREASED collagen and AA
INCREASED ATP:ADP ratio
What disorder is characterized by no alpha granules, large gray platelets with no granules, results from cardiopulmonary bypass and platelet aggregation studies are blunted with everything except ADP and epinephrine?
Gray Platelet syndrome
What is the dysfunction in Quebec platelet disorder?
No alpha granules (similar to gray platelet syndrome)
What disorder is X linked, NO DELTA GRANULES on EM, platlets are small and granulated and is characterized by thrombocytopenia, infection, eczema and increased risk of malignancy?
Wiscott Aldrich syndrome
(Chediak Higashi and Hermansky Pudlak also no delta granules)
Which three platelet disorders are characterized by no delta granules on EM?
Chediak Higashi, Wiscott Aldrich and Hermansky Pudlak
What platelet disorder is characterized by no delta granules on EM, increased pigment in reticuloendothelial cells, has swiss cheese platelets, patients have increased AK, nevi, tumors and pulmonary fibrosis and granulomatous colitis and increased vWF?
(Chediak Higashi and Wiscott Aldrich are also from no delta granules)
*Affected genes: HPS1 (10q23), HPS3, HPS4, HPS5, HPS6, AP3B1, DTNBP1
What will aspirin use show on platelet aggregation studies?
DECREASED second wave to ADP and epinephrine
ABSENT response to collagen and arachidonic acid
What coagulation factor is decreased in patients with amyloidosis?
What blood group has decreased vWF?
Blood Group O
vWF increased in exercise, inflammation, pregnancy and estrogen therapy
Newborns have high vWF activity; disease may not be detectable until 1 year of age
What diseases can give you secondary vWF deficiency?
Congenital heart disease
What vWF test is very specific and the most sensitive test and it measures vWF activity?
What type of vWD is characterized by low quantity, normal multimers, functionally normal, it is the most common type, sometimes all tests are normal, and is the only type treated w DDAVP?
Multimer analysis looks like normal, just every band is slightly decreased
What type of vWD is characterized by: decreased large and medium sized multimers and has a disproportionately low vWF:RCo (quality) relative to vWFAg (quantity)?
Multimer analysis shows decreased LARGE AND MEDIUM multimers (top)
What type of vWD is characterized by: mutation in exon 28 of VWF that causes increased affinity of VWF for GP1bα, decreased high molecular weight (HMW) multimers, leads to increase clearance of vWF, increased RIPA, No DDAVP?
To test: mutations in exon 28 of VWF gene
Multimer analysis: decreased high molecular weight
Must be distinguished from platelet type vWD where there is gain of function in GPIb receptor (here gain of function in vWF but result is same). The enhanced binding in both disorders causing increased clearance of platelets and high molecular weight multimers from the blood thus thrombocytopenia and decreased HMW multimers are characteristic in both disorders
What type of vWD is characterized by: only one to be autosomal recessive (others are AD), severe marked deficiency, absence of vWF, F8 also low, may have nl coag parameters, all multimers low and no DDAVP?
Results from frameshift mutations, nonsense mutations and deletions of the vWF gene
What type of vWD is characterized by: defect in GPIb binding (loss of function of GPIb receptor), but no loss of HMW multimers, vWF made but doesn’t work, decreased vWF:Rco, sometimes nl—RIPA, vWF Ag, and F8 and you should suspect when vwf:Rcof < vwf Ag?
What type of vWD is characterized by: defective binding of vWF to FVIII, hemophilia-like (but AR), women with low F8 think of this dz?
Tests: decreased FVIII, decreased vWFAg:C
levels, normal RIPA, nl multimers, nl ristocetin, normal sequence analysis of F8 gene to rule out hemophilia
Type 2N (Normandy)
On boards if you are given stem that sounds just like a hemophiliac but it is in a woman that has low factor VIII, pick this!
What is the order of frequency for the vWD?
What type of vWD is characterized by: mutations in GP1ba resulting in increased binding of GPIba to HMW VWF multimers, the abnormality is on the patients platelets (GP1b) not with vWF, plts bind large VWF multimers, VW multimer test shows decreased large vWF multimers, abn RIPA studies, platelet agg studies show low dose ristocetin aggregation, aggregation with cryoprecipitate?
Pseudo vWD (platelet type)
*mutations in GP1bα gene, whereas VWF 2B has mutations in exon 28 of VWF gene
What are the only two types of vWD that have abnormal RIPA tests?
Type 2B and platelet type!
What is the classic molecular finding in Hemophilia A?
Chr (Xq28), 50% intron 22 inversion
What is a Bethesda unit?
Bethesda assay is performed to determine the titer of anti VIII antibody
Plasma from pt is diluted and each dilution is mixed 1:1 with normal plasma and incubated 1-2 hours
Factor VIII assays are then performed on each dilution
The dilution at which the fVIII activity is 50% presents the inhibitor titer
Result expressed in Bethesda units (if the 1:16 dilution results in 50% factor activity, then the result is 16 Bethesda units)
Low titer antibodies (<5 BU) can usually be successfully treated with DDAVP and higher doses of human fVIII
What factor inhibitor can cause anaphylaxis when treated?
Which factor deficiency is characterized by decreased prekallikrein, increased PTT but NO bleeding, and has a prolonged mixing study?
*Decreased F12-Hageman so there is increased PTT but thrombosis
What factor deficiency is characterized by nl PT, nl PTT, cant crosslink fibrin, clot stability test-clot can’t stop 5M urea from dissolving clot < 24hrs, (nl>24hrs)?
Factor XIII deficiency
*on boards if you see 5M urea, think Factor XIII
Proteinuria will cause a decrease in what two coagulation factors?
Factors XI and XII
What disorder is characterized by patient presents with bleeding, but nl PT and nl PTT, decreased euglobulin lysis time--measures the time to dissolve a clot, decreased euglobulin lysis test <2hrs, also decrease in fibrinogen, DIC, increased tPA?
Alpha 2 antiplasmin deficiency
*if you see euglobulin test on exam, pick this!
What causes the platelets to clump in EDTA tube?
antibodies to GPIIb/IIIa causes plts to clump
*will normalize in sodium citrate tube
What are the two Factor V mutations in patients with activated protein C resistance?
1) Glt for Arg at position 506 (Factor V Leiden)
2) Arg for Threo at position 306 (Factor V Cambridge)
*In APC Resistance, can also have mutations in Factor II and MTHFR
How do you screen for activated protein C resistance?
Functional assay-(PTT resistance ratio)
• If patient does not have APCR and you add ProtC to
their specimen, increased PTT >2:1
• If patient has APCR and you add ProtC to their
specimen, increased PTT <2:1
If you see a picture of patient with MASSIVE skin necrosis in relationship to clotting disorder and coumadin, what is it?
Protein C Deficiency
Oral contraceptives, estrogen and pregnancy will decrease levels of what protein?
Protein C and antithrombin not effected
• Prot S is a cofactor to Prot C
– 60% Protein S binds to C4b binding protein
– Only 40% is free, that is the functional protein S
• C4b is an acute phase reactant, increased C4b, decreased protein S
– Thus decreased Prot S during stress (pregnancy)
If a patient has thrombosis and you treat with heparin but the PTT doesn't rise sufficiently, what should you suspect?
Antithrombin III Deficiency
*ATIII binds to heparin to inhibit Factors II and X, without ATIII, these factors go unchecked and you still have clotting
What is the mechanism behind prothrombin G20210A mutations?
• Point mutation leads to high prothrombin levels
• 20210 is the location of the mutation in the gene
• Guanidine to adenine substitution in the 3’ untranslated portion of prothrombin gene on Chr 11
Mutation present in 10% of those with factor V Leiden mutation. Risk of venous thrombosis, particularly cerebral vein thrombosis
What test is falsely positive in patients with antiphospholipid syndrome?
What are the only two things that show impaired ristocetin aggregation on platelet aggregation studies?
Bernard Soulier and vWD
What disorder is shown in this platelet aggregation study (no response to anything EXCEPT ristocetin and this is an incomplete response)?
Glanzmann's thrombasthenia or afibrinogenemia
*Remember, platelet agglutination with ristocetin occurs independently of fibrinogen and only partial agglutination is seen with ristocetin emphasizing that for aggregation to occur, binding of fibrinogen to the GpIIb/IIIa receptor is necessary
What two types of vWD show ENHANCED ristocetin induced platelet aggregation?
Types 2B and platelet type
What type of vWD is it CONTRAINDICATED to give DDAVP?
Will further increased vWF binding to GPIb resulting in microaggregate formation and sequesteration or clearance of platelets
Of the inherited combined factor deficiences, what is the most common and what mutation is responsible?
Combined Factor V and VIII
What gene mutation is responsible for antithrombin III deficiency?
the antithrombin gene
The antiphospholipid syndrome encompasses both lupus anticoagulant and anticardiolipin antibody syndromes. What are the major differences?
Arterial thrombosis (ACA has, LAC does not)
Prolonged PTT (LAC has, ACA does not)
Associated with livedo reticularis (ACA is, LAC is not)
Warfarin effective for long term prophylaxis (ACA ineffective, LAC effective)
What diseases can give false positive anticardiolipin antibody result?
Syphilis, Q fever, HIV
usually IgM ACA
In real ACA, high titer IgG ACA is thought to be significant
Patients with low titer IgG (<1:40) or who have solely IgM are not at significant risk for thrombosis but both types of patients have a high risk of developing high titer IgG later
In what scenario is anticardolipin antibody thought to be the most thrombotic?
When the ACA is specific to beta 2 glycoprotein I
It is thought that ACA specific to B2GPI antigen correlates most strongly with thrombotic risk
Which inherited platelet disorder hast he classical finding of "large peroxidase positive granules" in neutrophils?
What gene is associated with clopidogrel induced platelet dysfunction?
What is the most potent activator of platelets what receptor does it interact with?
Thrombin mediated by the thrombin-protease activated receptor 1 (PAR-1) interaction
What clotting factors are at elevated or normal levels in neonates compared to adults?
Fibrinogen, Factor VIII and vWF
What thrombotic disorders cause:
a) venous thrombosis only
b) arterial thrombosis and venous thrombosis
a) lupus anticoagulant, activated protein C resistance, protein C def, protein S def, ATIII def
b) anticardiolipin, prothrombin mutation 20210, HIT
What test can help distinguish between Type 2B vWD and platelet type vWD?
Platelet type will correct with the addition of cryoprecipate but Type 2B will not
What factor has the shortest and longest half life?
Shortest: Factor VII
Longest: Factor XIII
What deficiency causes PTT correction with a 1:1 mixing study then DECREASED PTT with incubation?
Factor XII, prekallikrein and HMWK deficiencies are not associated with bleeding
Complete normalization of PTT with incubation is characteristic of prekallikrein and is from autoactivation of factor XII (activation of XII to XIIa)
What is known to cause false positive result in activated protein C resistance screening test (ie increase protein C activity)?
*low protein S will do this as well but LAC will still cause this in the second generation screening assays which usually eliminate the false positive of low prot S
On the platelet, what is the collagen receptor as well as the Bra/Brb antigen?
On the platelet, what is the fibronectin receptor?
What are the platelet cell surface antigens?
- GPIb/V/IX complex (CD42)--receptor for vWF
- GPIIb/IIIa complex (CD41 and CD61)--receptor for fibrinogen GPIIIa is the basis for platelet antigens PLA1 and PLA2 and GPIIb is basis for antigens baka and bakb
- GPIa/IIa complex--collagen receptor and Bra/Brr antigen
- GPIc/IIa complex--fibronectin receptor
- Red cell antigens ABO, P, I, i and Le--no Rh antigens
- Class I MHC antigens--NO class II antigens
- IgG and coagulation factors--passively adsorbed onto platelet surface
What receptor is the basis for the platelet antigens PLA1 and PLA2?
What about baka and bakb?
GPIIIa is the basis for platelet antigens PLA1 and PLA2
GPIIb is basis for antigens baka and bakb
MUST KNOW COAGULATION CASCADE:
Explain the extrinsic pathway.
The main role of the tissue factor pathway is to generate a "thrombin burst", a process by which thrombin, the most important constituent of the coagulation cascade in terms of its feedback activation roles, is released very rapidly. FVIIa circulates in a higher amount than any other activated coagulation factor. The process includes the following steps:
Following damage to the blood vessel, FVII leaves the circulation and comes into contact with tissue factor (TF) expressed on tissue-factor-bearing cells (stromal fibroblasts and leukocytes), forming an activated complex (TF-FVIIa).
TF-FVIIa activates FIX and FX.
FVII is itself activated by thrombin, FXIa, FXII and FXa.
The activation of FX (to form FXa) by TF-FVIIa is almost immediately inhibited by tissue factor pathway inhibitor (TFPI).
FXa and its co-factor FVa form the prothrombinase complex, which activates prothrombin to thrombin.
Thrombin then activates other components of the coagulation cascade, including FV and FVIII (which forms a complex with FIX), and activates and releases FVIII from being bound to vWF.
FVIIIa is the co-factor of FIXa, and together they form the "tenase" complex, which activates FX; and so the cycle continues. ("Tenase" is a contraction of "ten" and the suffix "-ase" used for enzymes.)
Explain the intrinsic pathway.
The contact activation pathway begins with formation of the primary complex on collagen by high-molecular-weight kininogen (HMWK),prekallikrein, and FXII (Hageman factor). Prekallikrein is converted to kallikrein and FXII becomes FXIIa. FXIIa converts FXI into FXIa. Factor XIa activates FIX, which with its co-factor FVIIIa form the tenase complex, which activates FX to FXa. The minor role that the contact activation pathway has in initiating clot formation can be illustrated by the fact that patients with severe deficiencies of FXII, HMWK, and prekallikrein do not have a bleeding disorder. Despite this, interference with the pathway may confer protection against thrombosis without a significant bleeding risk.
Explain the common pathway.
The division of coagulation in two pathways is mainly artificial, it originates from laboratory tests in which clotting times were measured after the clotting was initiated by glass (intrinsic pathway) or by thromboplastin (a mix of tissue factor and phospholipids). In fact thrombin is present from the very beginning, already when platelets are making the plug. Thrombin has a large array of functions, not only the conversion of fibrinogen to fibrin, the building block of a hemostatic plug. In addition, it is the most important platelet activator and on top of that it activates Factors VIII and V and their inhibitor protein C (in the presence of thrombomodulin), and it activates Factor XIII, which forms covalent bonds that crosslink the fibrin polymers that form from activated monomers.
Following activation by the contact factor or tissue factor pathways, the coagulation cascade is maintained in a prothrombotic state by the continued activation of FVIII and FIX to form the tenase complex, until it is down-regulated by the anticoagulant pathways.
What are the regulators of the coagulation cascade?
Five mechanisms keep platelet activation and the coagulation cascade in check. Abnormalities can lead to an increased tendency toward thrombosis:
Protein C is a major physiological anticoagulant. It is a vitamin K-dependent serine protease enzyme that is activated by thrombin into activated protein C (APC). Protein C is activated in a sequence that starts with Protein C and thrombin binding to a cell surface protein thrombomodulin. Thrombomodulin binds these proteins in such a way that it activates Protein C. The activated form, along with protein S and a phospholipid as cofactors, degrades FVa and FVIIIa. Quantitative or qualitative deficiency of either (protein C or protein S) may lead to thrombophilia (a tendency to develop thrombosis). Impaired action of Protein C (activated Protein C resistance), for example by having the "Leiden" variant of Factor V or high levels of FVIII also may lead to a thrombotic tendency.
Antithrombin is a serine protease inhibitor (serpin) that degrades the serine proteases: thrombin, FIXa, FXa, FXIa, and FXIIa. It is constantly active, but its adhesion to these factors is increased by the presence of heparan sulfate. Quantitative or qualitative deficiency of antithrombin (inborn or acquired, e.g., in proteinuria) leads to thrombophilia.
Tissue factor pathway inhibitor (TFPI) limits the action of tissue factor (TF). It also inhibits excessive TF-mediated activation of FVII and FX.
Plasmin is generated by proteolytic cleavage of plasminogen, a plasma protein synthesized in the liver. This cleavage is catalyzed by tissue plasminogen activator (t-PA), which is synthesized and secreted by endothelium. Plasmin proteolytically cleaves fibrin into fibrin degradation products that inhibit excessive fibrin formation.
Prostacyclin (PGI2) is released by endothelium and activates platelet Gs protein-linked receptors. This, in turn, activates adenylyl cyclase, which synthesizes cAMP. cAMP inhibits platelet activation by decreasing cytosolic levels of calcium and, by doing so, inhibits the release of granules that would lead to activation of additional platelets and the coagulation cascade.
In platelet aggregometry, what are the reasons for the following results:
a) poor response to all agents except ristocetin
b) absent secondary phase with epinephrine and ADP
c) poor response to epinephrine
d) reponse to everything but ristocetin
e) aggregation blunted with all agents except ADP
a) Glanzmann thrombasthenia
b) storage pool disorders and aspirin
c) myeloproliferative disorders
d) von Willebrand disease and Bernard Soulier (failure to aggregate in the presence of normal plasma distinguishes the two)
e) gray platelet syndrome
What is the activated clotting time?
Usually a point of care test used to monitor high dose heparin therapy (often used in cardiopulmonary bypass)
Performed on whole blood--blood is collected in tube that contains an intrinsic pathway activator (kaolin, glass, etc) and an analyzer measures the clotting time
Not as reliable at aPTT or anti Xa assay--influenced by a large number of noncoagulation parameters including hypothermia, hemodilution and platelet defects
What factors does aged plasma lack? Serum? Adsorbed plasma?
Aged and serum: II, V, VIII, XIII
*serum lacks all of these plus fibrinogen
Adsorbed: II, VII, IX, X
What is the intended anticoagulant ratio in coagulation testing?
3.2% trisodium citrate in collection tubes (~0.5mL) is intended to result in a final ratio of whole blood to anticoagulant of 9:1 and a ratio of plasma to anticoagulant of 5:1 assuming normal hematocrit (35-55%)
High hematocrit = less plasma so over anticoagulated
Underfilling = over anticoagulated, Overfilling = under coagulated
*plasma should be separated from cells as soon as possible because plts begin to release PF4 which can shorten PTT
anti Xa assay unlike PTT is unaffected by underfilled tubes and abnormal factor levels
*plasma should be kept cool until testing to minimize loss of coag factors; if delayed >4hrs specimen should be frozen
*normal neonate has a PTT up to 55 seconds which shortens to adult range by 6 months of age
What is the chromogenic factor X assay useful for?
This is different from anti Xa assay
Useful for monitoring warfarin in the presence of lupus anticoagulant, hirudin or argatroban
What percent of hemophilias have a negative family history and are due to new mutations?
What platelet disorder shows diminished in vitro clot retraction?
What is Factor IX Leiden?
Type of hemophilia B characterized by spontaneous remission following puberty
Can the hemophilias be diagnosed at birth?
Hemophila A can: FVIII levels normal in neonates
Hemophilia B cannot: FIX levels are low in neonates
What factor deficiency is a common finding in Noonan syndrome?
What gene is responsible for inherited hyperhomocysteinemia?
MTHFR gene mutation called the T allele (C677T)
Regarding the antiphospholipid syndromes (anticardiolipin and lupus anticoagulant), what features are found mainly in anticardiolipin?
Premature coronary atherosclerosis
Postpartum syndrome: fever, pleuritic chest pain, pleural effusion, patchy pulmonary infiltrates, cardiomyopathy and ventricular arrhythmias
What drug is a direct Xa inhibitor, binds AT and promotes inactivation of Xa but does not enhance inactivation of thrombin? Monitored using the aPTT and cannot be reversed with protamine
Apixaban and Rivaroxaban (ORAL)
What are the direct thrombin inhibitors that inhibit thrombin without AT and used to treat patients with HIT?
What platelet drugs block the P2Y12 receptor that mediates ADP inducted platelet activation?
Ticlopidine and Clopidigrel
What platelet drug works through downstream effects of phosphodiesterase inhibition and reduces intracellular calcium concentrations?
in combo with aspirin is marketed as Aggrenox
What platelet drugs are the GPIIb/IIIa antagonists?
How does the tissue factor pathway inhibitor inhibit coagulation?
Inhibition of tissue factor-factor VIIa-factor Xa complex
What platelet cell surface marker is aberrantly unstimulated with high dose thrombin in patients with gray platelet syndrome?
In addition there is also decreased PF4 expression on the surface of platelets.
All of the following factors are inhibited by antithrombin EXCEPT:
b) factor IXa
c) factor Xa
d) factor XIIa
e) factor Va
e) factor Va
To remember: AT inhibits thrombin (II), IX, X, XI and XII (9, 10, 11 and 12)
What are the patients with homozygous protein C deficiency particularly at an increased risk of developing?
They also get warfarin skin necrosis but this is the awful extreme form of that
What is the most common cause of antiphospholipid sydrome (ACA or LAC)?
The vast majority are ACA, the rest are LAC
What is an acquired cause of Factor VII deficiency?
Acquired causes of Vit K def (IBD, antibiotic therapy, diet, TPN), liver disease and warfarin therapy
The one stage coagulation assay is an example of a parallel line bioassay. In this type of assay, the results are reliable when the curves of reference and patient plasma are parallel. If there is non-parallelism what should be considered?
Inhibitors (LAC or others)
If three or more patient dilutions are used and they do not agree within a set tolerance limit, the assay is demonstrating an inhibitor pattern. A chromogenic factor assay should be performed.
What is the lab criteria to diagnose lupus anticoagulant?
LAC present in plasma on two or more occasions at least 12 weeks apart
ACL antibody or IgG and/or IgM isotype in serum or plasma present in medium or high titer on two or more occasions at least 12 weeks apart
Anti beta 2 glycoprotein 1 antibody of IgG and/or IgM isotype in serum or plasma, present on two or more occasions at least 12 weeks apart
What are the inherited thrombocytopenias that are associated with SMALL platelets?
Wiskott Aldrich syndrome
Congenital Amegakaryocytic Thrombocytopenia (CAMT)
Thrombocytopenia with Absent Radius (TAR)