Flashcards in Ch. 4 - Hemostasis and Related Disorders Deck (261):
primary hemostasis forms a..
weak PLT plug
secondary hemostasis stabilizes the PLT plug with...
PLTs bind vwF via what receptor?
vwF binds exposed..
What is the FIRST thing that happens when the endo has been damaged?
reflexive vasoconstriction via neural response and endothelin
What are the two sources of vWF?
Weibel-Palade bodies of endo and a-granules of PLTs
What are the two mediators that are released from PLTs adhesed to vWF?
ADP is released from what granule in the PLT?
ADP release from PLTs promotes the exposure of what receptor on the PLT?
how do PLTs aggregate together?
TXA2 is synthed by what enzyme?
what is the linker molecule between GPIIb/IIIa receptors?
What are the major symptoms of disorders in PRIMARY hemostasis?
MUCOSAL BLEEDINGepistaxis, hemoptysis, GI bleeding, hematuria, meorrhagia
what is a severe complication o thrombocytopenia?
Describe the size of petehcia, purprua and echymoses
petechiae: 1-2mmpurpura: >3mmecchymoses: >1cm
Are petechiae seen in QUALITATIVE d/o of bleeding?
NO just when PLTs are low!!!
what is the most common cause of thrombocytopenia in adults and kids?
ITPimmune thrombocytopenic purpura
Describe the general process of ITP
autoAbs produced by the spleen; coat PLTs, the spleen then eats the complex
what cell in the spleen produces the autoAbs in ITP?
after what event does acute ITP surface?
acute viral infection or IMMUNIZATION; self limited
What type of Ig is involved in ITP?
Chronic ITP is assc'd with other autoDz like....
how can newborns get ITP?
IgG can cross the placenta from mom with ITP/SLE
What is the PT/PTT like in ITP?
NORMAL; just not ENOUGH PLTs!
how does the bone marrow look in ITP?
what is the initial Tx for ITP?
What is the Tx for symptomatic bleeding in ITP?
IVIG; just buys you time
What is the ultimate Tx for ITP?
splenectomy; removes the source of Abs and cuase of PLT destruction
What is the ultimate Tx for ITP?
splenectomy; removes the source of Abs and cuase of PLT destruction
What causes the shearing of RBCs in MAHA?
formation of microthrombi
TTP is due to decreased (blank), an enzyme that cleaves vWF for degradation
TTP is due to decreased (blank), an enzyme that cleaves vWF for degradation
MAHA is seen in what two qualitative PLT disorders?
TTP and HUS
Is decreased ADAMTS13 levels a congenital or acquired def?
acquired strangely enough!; seen in adult females
(TTP/HUS) is caused by drugs or infection
What E. coli toxin damages endothelial cells in the kidney and brain in HUS?
E. coli verotoxin
What are the common clinical findings in TTP/HUS?
1. skin and mucosal bleeding2. MAHA3. fever
What clinical finding lets you know you have HUS and TTP?
What clinical finding lets you know you have TTP and not HUS?
What are the lab values for TTP and HUS:PLTbleeding timePT/PTTHgbPeripheral smearBone marrow biopsy
low PLTincreased bleeding timenomral PT/PTT; coag cascade not involved!!!low Hgb aka anemiaschistocytes on smearincreased megakaryocytes on bone marrow biopsy
Bernard-Soulier syndrome is due to a genetic (blank) deficiency causing impaIred platelet ADHESION
What finding do you see on smear in Bernard-Soulier syndrome?
enlarged PLTs; Big-Suckers
Glanzmann thrombasthenia is a genetic (blank) deficiency causing impaired PLT AGGREGATION
Aspiriin irreversibly inhibits COX leading to a lack of (blank) and impairs aggregation
T/F: both adhesion and aggregation are impaired in uremia
secondary hemostasis generates (blank) which stabilizes the PLT plug
Thrombin converts fibrinogen to (blank)
The formation of fibrin allows it to be (blanked) to generate strength
Where are the coagulation factors produced?
in the liver
T/F: coag factors are produced in an inactive state
What is the activating substance for the extrinsic (activates VII) pathway?
tissue thromboplastin (TT)
What is the activating substance for the intrinsic (activates XII) pathway?
subendothelial collagen (SEC)
What are the three things needed to activate the coag cascade?
1. activating factor (SEC or TT)2. phospholipid surface of PLTs3. Calcium from PLT dense granules
What distinguishes 2ry hemostatic disease from 1ry?
2ry causes deept tissue bleeding into muscles and joints (hemarthrosis) and rebleeding after surgical procedures (circumcision and tooth extraction common)
What factors are in the intrinsic pathway?
12, 11, 9, 8
What factors are in the extrinsic (tissue factor) pathway?
7; 7 is lucky, luck is extrinsic
What factors are in the common pathway?
5, 2, 1
What factors are activated by Vit. K?
2, 7, 9, 10, C, S
(PT/PTT) measures the extrinsic pathway (7)
PT; TT activates 7, PT and TT both have 2 letters
(PT/PTT) measures the intrinsic pathway (12)
PTT; SEC activates 12, PTT and SEC both have 3 letters
Hemophilia A is caused by a def of what factor?
What is the mode of inheritance in males of hemophilia A?
T/F: hemophilia A can present with no family history
What is the most common presentation of hemophilia a?
deep tissue bleeding after surgery
T/F: severity of hemophilia A is in a range depending on how def you are
What are the lab values for hemophilia a?PT/PTTfactor levelsPLTbleeding time
HI PTTnormal PTlow FVIIINORMAL PLTnormal bleeding time (if superficial can use primary hemostasis)
How do you treat hemophilia A?
What is Christmas disease ?
hemophilia B, factor 9 def
What is the only difference between hemophilia A and B?
B has a 9 def
T/F: a mixing study will normalize the PTT in both hemophilia a and B
T/F: a mixing study will normalize PTTT in a coagulation factor inhibitor
FALSE; factor will overwhelm the mixed serum
What is the most common anti-factor inhibitor?
T/F: inhibitor disorders can cause qualitative and quantitative disorders
What is the most common INHERITED coag disorder?
How does vW disease normally present?
mild skin and mucosal bleeding
vW disease is due to impaired PLT (adhesion/aggregation)
Describe the lab values for vW diseasebleeding time PT/PTTPLT Ristocetin test
increased bleeding timeincreased PTT: decreased FV8 b/c vWF stabilizes 8normal PTabnormal ristocetin leading to NO agglutination
What is the Tx for vW disease?
Desmopressin increases vWF release from the (blank) bodies of endothelial cells
Vit. K is activated by (blank) in the liver
Vit. K gamma carboxylates what factors?
2 7 9 10 C S
PT is used to test (heparin/coumadin) levels
PT = coumadin/warfrintwo letters, two drug names
PTT is used to test (heparin/coumadin)
PTT = heparin; HEParin has three letters like PTT
Coumadin blocks (blank) activity resulting in less activated Vit. K
what are the three scenarios in which you see a Vit. K def?
1. newborns --lack of GI bacteria to make vit. K2. long term abx therapy3. malabsorption
How does liver failure lead to problems with the coag cascade?
Liver is the source of all the factors AND of Vit. K activation. DECREASED PRODUCTIONDECREASED ACTIVATION
How does a large volume transfusion mimmic a coag cascade def?
Works to dilute the factors
WHat is another name for factor I?
What is another name for prothrombin?
What coag factor is made by the Kuppfer cells in the liver?
WHere is Prekalikrein made?
Where is high molecular weight kininogen made?
What is another name for factor XIII
fibrin stabilizing factor
What is Hagemann factor?
What is christmas factor
What is antihemophilic factor?
What two factors make up the prothrombinase complex?
Va and Xa
What three factors make up the tenase complex?
VIIIa, Xa, and Ca
What two factors are needed to convert XII to XIIa?
prekallikrein and high molecular weight kininogen
What ion is needed to transform VIIIa to X?
What factor is needed to take cross link fibrin?
What factor is needed to take Fibrinogen to fibrin?
Plasmin degrades what end product of the coag cascade?
what coag path is activated by tissue injury?
Extrinisc via 7
Which coag path is activated by contact?
What test is done by adding phospholipid (contact activator) to calcium and plasma?
What test is done by adding tissue factor and phospholipid to plasma?
What test screens for qualitative PLT disorders?
What disease presents with this PENTAD of symptoms:1. thrombocytopenia2. hemolytic anemia3. neurologic abn.4. renal abn.5. fever
what is the mode of inheritance of activated protein C resistance?
(blank) is responsible for 50% of hereditary thrombophilia
activated protein C resistance
What is the MOA of activated protein C resistance? (think Factor V)
heterozygosity of FV Leidin which makes FVL resistance to inactivation via protein C
An anthithrombin deficiency leads to no inactivation of what factors?
II, IXa, Xa, XIa, XIIIa2 9a 10a 11a 12a
what is the MOA of anthithrombin?
Protein C is activated by the (blank) complex
What is the cofactor for the thrombin-thrombomodulin complex?
Acquired (blank) deficiency may be due to coumadin therapy, liver disease, and pregnancy
Antiphospholipid syndrome includes what two antibodies?
lupus anticoagulant syndromeanti-cardiolipin syndrome
In what diseases do you seen antiphospholipid syndrome?
lupus, primary APL syndrome, HIV, malignancy, collagen vascular disorders, and with drugs
What is the second most common causes of inherited thrombophilia?
thrombin can act on what activated factors?
2a 9a 10a 11a 12a
Is the protein C receptor antithrombotic or prothrombotic?
Is tPA antithrombotic or prothrombotic?
Is Thromboxane antithrombotic or prothrombotic?
Are NO and prostacyclin antithrombotic or prothrombotic?
What platelet receptor binds vWF?
What platelet receptor binds fibrinogen?
What platelet receptor binds fibronectin?
What platelet receptor is an adhesion molecule?
What platelet receptor binds initiates platelet activation when bound by thrombin?
What platelet receptor binds initiates PLT activation when bound by ADP?
What platelet receptor binds collagen?
T/F: PLTs contain red cell antigens
T/F: PLTs contain Rh factor
What class of MHC ag is present on PLTs?
What particular MHCs are present on PLTs?
HLA-A, B, and C
What is contained within the dense granules of PLTs?
What is contained within the a-granules of PLTs?
vWFFibrinogenFVVEGF, EGF, PDGFAngiostatin, thrombospondin, endostatinPF-4, IL-8, CCL5
PGI2 released by endothelial cells has a (pos/neg) effect on the coag cascade
Tissue Factor Pathway Inhibitor blocks what conversion?
7 to 7a
tPA prevents what final step of stabilizing the PLT plug?
cross linking of fibrin;tpA converts plasminogen to plasmin, and plasmin blocks the cross linking
What test do you use to screen for vW disease?
T/F: bleeding time is useful to predict the risk of bleeding during surgery
What test uses ADP, epi, arachidonate, collagen, and ristocetin to determin PLT aggregation?
What is PLT flow cytometry used to Dx?
def. of PLT surface glycoproteins and disorders of PLT activation
INR is used to monitor (heparin/coumadin) therapy
INR references the (PT/PTT)
What test is used to monitor heparin, hirudin, or argatroban therapy?
What test is used to test the presence of functional fibrinogen?
What causes prolongation of the thrombin time?
heparin, hirudin, argatroban and dysfribrinogenemia
What does a mixing study screen for?
presence of inhibitors
T/F: mixing studies excludes the presence of heparin
If there is at least 50% activity on the mixing study, then you know that the prolongation is due to (blank)
a factor deficiency
If there is less than 50% activity in the mixing study, then you know that the prolongation is due to (blank)
presence of an inhibitor
D-dimers are formed by the degradation of what molecule in the clot?
The fuck do you use an Anti-Xa assay for?
monitor unfractionated or LMWH therapy
Males tend to have (coag/PLT) bleeding disorders
females tend to have (coag/PLT) bleeding disorders
Type I vW disease is (quantitative/qualitative) disorder
quantitative; not enough vWF
Describe the lab values for Type I vW disease:PTPTTBT (bleeding time)FVIII levels
normal PTincreased PTTincreased bleeding timedecreased FVIII
Type II vW disease is (quantitative/qualitative)
Type IIM vW prevents vWF from binding to (blank)
Type IIN vW is shows reduced binding of vWF to (blank)
Type IIa vW is absence of (blank)
high molecular wt. vWF multimers
What is the only lab value that is markedly changed in vWF IIa?
ristocetin agglutination decreased
vW disease IIb is spontaneous binding of vWF to (blank)
T/F: vW IIa and IIb both have decreased high molecular wt. vWF multimers
What should you not give to someone with vW IIb?
DDAVP: profound thrombocytopenia and bleeding
What is wonky about the ristocetin test in vW IIb>?
it is increased since there is spontaneous PLT binding
In what disease do PLTs lack the PLA1 ag?
IN what disorder to PLTs fail to aggregate with all agonists except risocetin?
Hermansky-PudlakChediak-HigashiWiskott-AldrichAre all (blank) diseases with no second wave of aggregation
In alpha granule disease, aggregation is blunted with all agents except (blank)
Gray PLT syndrome is a (a/dense) granule disorder
ASA and NSAIDS inhibit what enzyme?
What molecule released by first wave PLTs from the dense granules signal for the second wave aggregation?
Is the effect of ASA or NSAIDS on COX-1 irreversible?
Ticlopidine and Clopidogrel inhibit (blank) mediated PLT activation
Abciximab, Eptifibatide, Tirofiban inhibit the (blank) receptor, aka fibrinogen receptor
Abciximab, Eptifibatide, Tirofiban will cause impaired aggregation to which agonists?
all except ristocetin
Ticlopidine & Clopidogrel will cause impaired aggregation against which agonist?
What bleeding disease is made by a diagnosis of exclusion?
Heparin induced thrombocytopenia is IgG binding to what complex?
Heparin-PF4 between the drug and the PLT
T/F: bleeding is rare in HIT
T/F: thrombosis is likely in HIT
true, as strange as it is considering the name; PLTs will aggregate and activate the fucking cascade
Liver disease results in chronic DIC from an impaired clearance of (blank)
anti-thrombin def. results in (arterial/venous) thromboses
T/F: homozygous anti-thrombin def is incompatible with life
antibodies against B2 glycoproteins and prothrombin are most likely what type of Ab?
antiphospholipid; can be classified as lupus anticoagulant or anticardiolipin
phenytoin, quinidine, hydralazine, procainamide, phenothiazines, IFN, cocainecan all cause secondary (blank)
Coumadin therapy may result in an acquired (blank and blank) def
protein C and S
Ca is necessary in the conversion of what factor from the intrinsic pathway to the common pathway?
8a to X
What PLT surface marker can HEP bind to?
What causes PLT destruction in heparin induced thrombocytopenia?
IgG binding to HEP-PF4
What activates the PLTs in HIT?
the fragments of the destroyed PLTs, leading to thrombosis
DIC can lead to (blank) of downstream tissue
infarction and ischemia
Where do you see bleeding in DIC?
IV sites and mucosal surfaces
How does pregnancy cause DIC?
TT from the amniotic fluid may initiate coag cascade
Sepsis from what two bugs can cause DIC?
E. coli and N. meningitidis
Macrophages release what two cytokines during sepsis that can lead to DIC?
TNF-a and IL-1
What is is about infx with E. coli and N. meningitidis that leads to DIC?
release of endotoxins
(blank) from adenocarcinoma can lead to DIC
Primary granules that go on to form Auer rods in (blank) can cause DIC
Acute promyelocytic leukemia
what kind of snake bite can cause DIC?
What are the lab values for DIC?PLTPT/PTTfibrinogenwhat type of anemia
LOW PLT (lots of little clots)INCREASED PT AND PTT (consumption of cascade)decreased fibrinogen (making clots)MAHA
What is the best test to screen for DIC?
Are d-dimers formed from the splitting of fibrin or fibrinogen?
fibrin; FROM LYSIS OF ALREADY PRESENT CLOT
Besides addressing the underlying condition causing the DIC, what supportive care can you give the patient?
transfusion of cryoprecipitate
What converts plasminogen to plasmin?
Plasmin cleaves (blank) and serum (blank), destroys coagulatoin factors, and blocks platelet (aggregation/adhesion)
cleaves fibrin and serum fibrinogenblocks PLT aggregation
What inactivates plasmin?
A radical prostatectomy resulting in large releases of urokinase or cirrhosis of the liver resulting in decreased a2-antiplasmin can both result in increased (blank)
What other disorder do issues of fibrinolysis resemble clincally?
Describe the labs for fibrinolytic disorders:PT/PTTbleeding timePLTD-dimers (present/absent)
increased PT/PTTincreased bleeding timeNORMAL PLTS; THERE ARE NO CLOTS, JUST ACTIVATION OF CLOT BUSTERNO D-DIMER BECAUSE NO ACTUAL CLOTS
What is the Tx for issues of tPA overdose or fibrinolytic disorders?
aminocaproic acid, blocks activation of plasminogen
T/F: a thrombus may occur in an artery or vein
Where do DVTs normally occur?
below the knee
DVTs are characterized by lines of (blank) and attachment to the vessel wall
lines of Zahn
what are the three risk factors for thrombus that makeup Virchow's triangle?
1. disruption in blood flow2. endothelial cell damage3. hypercoagulable state
T/F: turbulent non-laminar blood flow can cause clot formation
Immobilization, cardiac wall dysfunction, and anuerysm are all things that cause a (blank) in blood flow
Endothelial cells prevent thrombosis by protecting expsoure to subendothelial (blank) and underlying tissue factor
What two molecules do the endothelial cells produce that prevent thrombosis?
PGI2 and NO; PGI2 is opposite of TXA2 and NO causes vasodilation
Endothelial cells secrete heparin-like molecules that augment (blank) which inactivates thrombin and coag factors
What are the three actions of tPA?
1. converts plasminogen to plasmin2. cleaves fibrin and serum fibrinogen and destroys coag factors3. blocks PLT aggregation
Atherosclerosis, vasculitis, and high levels of (blank) can cause endothelial damage
What two vitamin defs can lead to high homocysteine?
Vit. B12 and folate def
What enzyme deficiency can lead to homocysteine buildup?
Chystathionine beta synthase (CBS)
Vessel thrombosis, mental retardation, lens dislocation, long slender fingers, and high levels of homocysteine are indicative of what congential enzyme def?
Hypercoagulable states are due to excess (blank) or deficiencies of (blank)
excess procoagulants or def. anticoags
DVTs normally ocurr below the knee or in what two arteries?
hepatic and cerebral
Protein C or S def decreases (neg/pos) feedback on the coag cascade
negative, they are ANTICOAGS
What factor do proteins C and S inactivate?
Protein C and S def has an increased risk of what drug reaction?
warfarin skin necrosis
Warfarin works by decreasing Vit. K dependent factors. Why does a protein C or S deficiency cause concern at the beginning of warfarin Tx?
The half life of C and S is shorter than that of the 2 7 9 10; therefore the anticoags disappear faster than the coags and the pt is at risk of a microvessel thrombus
What is Factor V Leidin?
FV that lacks the cleavage site for C and S
What is the most common cause of hypercoagulable state?
Factor V Leidin
An inherited point mutation that increases prothrombin expression is caused by (blank)
ATIII def decreases the effect of what class of molecules released by the endothelium?
heparin like molecules
What is unique about the PT/PTT in ATIII def when treating with heparin?
PTT does not rise with standard heparin dosing ATIII def; since aTIII is bound by HEPARIN-like molecules, the action of heparin is going to be limited!!
Once high doses of heparin are given to acheive an anticoag'd state in ATIII def pts, what is given to maintain their blood viscosity?
The pill increases a hypercoagulable state via what mechanism?
estrogen increases the production of coagulation factors.
What is the most common type of embolus?
What histo finding is characteristic of an atherosclerotic embolus?
cholesterol clefts in the embolus
a (blank) embolus is common after traumatic bone fractures (long bones) and soft tissue trauma
soft tissue trauma
in relation to the trauma, when does a fat embolus form?
while trauma is still present or during repair
What clinical findings are associated with a fat emoblus/
SOB, and skin petechiae on the CHEST
(blank) emobolus is seen in decompression sickness
What is the chronic form of gas embolus that causes multifocal ischemic necrosis of bone/
Gas embolus may also form during what type surgery?
Amniotic fluid is rich in what coagulation precursor?
Amniotic fluid emboli present with what symptoms as they travel the lung, brain, and systemically?
SOB, neurologic symptoms, DIC
Squamous cells and keratin debris in the embolus is characteristic of what?
amniotic fluid embolus
PE normally arises from a DVT in the lower extremity involving what three veins?
1. femoral2. iliac3. popliteal
T/F: PE is normally clinically silent
true, b/c the lung has dual blood supply
What percent of PEs result in infarction?
10%; need pre-existing compromise!
what symptoms do pts with PE have?
SOB, hemoptysis, pleuritic chest pain, pleural effusion
Describe the labs for PE:V/Qspiral CTLower extremity USD-dimer
V/Q mismatch; perfusion is abnormalCT shows vascular filling defectUS shows a DVTelevated D-dimer because they are trying to lyse the PE AND the DVT!!
What type of embolus in PE causes sudden death?
saddle embolus; death by electromechanical dissociation
WHat happens with chronic pulmonary emboli?