02 Hematology Flashcards
which type of VWD is most severe?
III. most severe bleeding
where do hemophiliacs tend to bleed?
joints.
will newborns with hemophilia A bleed at circumcision?
No. Factor VIII crosses placenta.
what is the best coagulation measurement for liver synthetic function?
PT
what does prostacyclin do?
decreases platelet aggregation and promotes vasodilation
what does thromboxane do?
increases platelet aggregation and promotes vasoconstriction (antagonistic to prostacyclin). also triggers release of calcium from platelets –> exposes GpIIb/IIIa receptor and causes platelet to platelet binding; platelet to collagen binding via Gp1b receptor
what are coagulation factors?
cryoprecipitate, FFP, DDAVP
what causes type I vWD? what is the treatment?
reduced quantity of vWF, treat with recombinant VIII:vWF, DDAVP, cryo
what are PTT and PT in hemophilia A?
high PTT, normal PT
what do you need to make sure in hemophilia A people before surgery?
need VIII 100% pre-op, keep at 80-100% for 10-14d after surgery
what INR is contraindication for central line placement, percutaneous needle bx, and eye surgery?
INR >1.3
what INR is contraindication for surgical procedures?
INR > 1.5
what are the players in fibrinolysis?
tissue plasminogen activator, plasmin, alpha-2 antiplasmin.
what causes type III vWD? what is Rx?
complete vWF deficiency (rare). Rx is VIII:vWF, cryoppt. (DDAVP doesn’t work)
what is active clotting time (ACT) for routine anticoagulation and for cardiopulmonary bypass?
150-200 sec for routine, >460 for cardiopulm bypass
what does thrombin do?
it is the key to coagulation. converts fibrinogen to fibrin and fibrin split products, activates factors V and VIII, activates platelets
should you aspirate hemophiliac joint bleeds?
no! give ice, keep joint mobile with range of motion, give factor VIII concentrate or cryoppt
what test do you do to figure out VWD?
ristocetin test (bleeding time)
where does thromboxane come from?
platelets
what are the symptoms of hemophiliacs?
epistaxis, ICH, hematuria. treat with recombinant factor VIII or cryo
what should PTT be for routine anticoagulation?
60-90 sec
can PT and PTT be normal in VWD?
yes. can be nl or abnl
what is the most common cause of surgical bleeding?
incomplete hemostasis
what is the function of vWF?
links GpIb receptor on platelets to collagen
what does tissue plasminogen activator do?
it is released from endothelium and converts plasminogen to plasmin
where does prostacyclin come from?
endothelium
when does FFP take effect and how long does it last?
immediately, lasts 6 hrs
what does alpha-2 antiplasmin do?
it is a natural inhibitor of plasmin, released from endothelium
what is definition of hemophilia A?
VIII deficiency
what does ATIII do?
key to anticoagulation, binds and inhibits thrombin, inhibits factors IX, X, XI, heparin activates AT-III (up to 1000x normal activity)
which is the only factor not synthesized in liver?
factor VIII. it’s synthesized in the endothelium
what does PTT measure?
measures most factors except VII and XIII (does not pick up factor VII deficiency). also measures fibrinogen.
what do DDAVP and conjugated estrogens do?
cause release of VIII and vWF from endothelium. similar effect as cryoppt
what does plasmin do?
degrades factors V, VIII, fibrinogen, fibrin –> lose platelet plug
what does protein S do?
vitamin K dependent, protein C cofactor
what does protein C do?
vitamin K dependent. degrades factors V and VIII, degrades fibrinogen
what does PT measure?
II, V, VII, X, fibrinogen.
what is in FFP?
high levels of coagulation factors, protein C, S, and AT-III
what is the normal half life for RBCs, platelets, and PMNs?
RBC: 4 months, platelets 7d, PMNs: 1-2d
what is another name for factor II?
prothrombin
which factor has the shortest half life?
factor VII
what is in cryoppt? when is it used?
high vWF-VIII. used for vWF disease and hemophilia (factor VIII deficiency). also has high levels of fibrinogen.
what factor is missing in hemophilia B?
IX
how is hemophilia A transmitted?
sex-linked recessive
what causes type II vWD? what is the treatment?
defect in vWF molecule itself, vWF does not work well. Rx is recombinant VIII:vWF, cryoppt
how many hours does vitamin K take to have effect?
6hrs
what is the most common congenital bleeding disorder?
VWD
which proteins in anticoagulation cascade vitamin K dependent?
proteins C and S, II, VII, IX, X
what is the most common type of VWD?
Type I (70% of cases), only mild sx
which factor is labile, lost activity in stored blood, and who continues to have activity in FFP?
factors V and VIII
what causes glanzmann’s thrombocytopenia?
GpIIb/IIIa receptor deficiency on platelets (can’t bind to each other). Fibrin normally links GpIIb/IIIa receptors together. Rx is platelets.
what causes bernard soulier?
Gp1b receptor deficiency on platelets (can’t bind collagen). vWF normally links GpIb to collagen. Rx is platelets
when does ASA need to stop before surgery?
7 days
what are the platelet disorders?
acquired thrombocytopenia, glanzmann’s thrombocytopenia, bernard-soulier, uremia
how does uremia induce thrombocytopenia? what is the treatment?
inhibits platelet fxn. Rx is hemodialysis (1st), then DDAVP, platelets
does LMWH have a decreased risk of HIT?
yes
what is PT and PTT in factor VII deficiency?
prolonged PT, normal PTT.
what are findings in DIC?
decreased platelets, low fibrinogen, high fibrin split products, high D-dimer, prolonged PT and PTT
what are lab findings in pts taking ASA?
prolonged bleeding times
what causes acquired thrombocytopenia?
H2 blockers, heparin
how is hemophilia B transmitted?
sex linked recessive
what is treatment for DIC?
treat underlying cause (eg sepsis)
high or low doses of heparin to cause HIT?
can occur with low
what is treatment for HIT?
stop heparin, start argatroban (direct thrombin inhibitor) to anticoagulate
what are PT and PTT in hemophilia B pts?
prolonged PTT, normal PT. same as hemophilia A.
how do you treat hemophilia B?
recombinant factor IX, or FFP
what is treatment for factor VII deficiency?
recombinant factor VII concentrate or FFP
how does HIT cause thrombocytopenia?
antiplatelet antibodies (IgG PF4 antibody) resulting in platelet destruction, platelet aggregation (thrombosis), forms a white clot.
what levels of IX do you need in a hemophilia B pt before surgery?
100% preop, keep at 30-40% for 2-3d after surgery
what are the three initial responses to vascular injury?
vasoconstriction, platelet adhesion, thrombin generation
what is the extrinsic pathway?
exposed collagen + prekallikrein + HMW kiniogen + factor XII activate XI –> activate IX, then add VIII –> activate X, then add V –> convert prothrombin (factor II) to thrombin –> thrombin then converts fibrinogen to fibrin
what does fibrin do?
links platelets together (binds GpIIb/IIIa molecules) to form platelet plug –> hemostasis
what is the intrinsic pathway?
tissue factor (injured tissues) + factor VII –> activate X, then add V –> convert prothrombin to thrombin –> thrombin then converts fibrinogen to fibrin
what does tissue factor inhibitor do?
inhibits factor x
what causes warfarin induced skin necrosis?
when pt placed on coumadin without being heparinized first
what causes warfarin-induced skin necrosis?
short half life of proteins C and S –> decrease in levels compared with the procoagulation factors; results in relative hyperthrombotic state.
who is especially susceptible to warfarin-induced necrosis?
pts w relative protein C deficiency
how do you treat warfarin-induced skin necrosis?
heparin if it occurs. prevent by placing pt on heparin before starting warfarin
what are the elements in deveoping venous thromboses? what is it called?
virchow’s triad: stasis, endothelial injury, hypercoagulability
what are the key elements in development of arterial thrombosis?
endothelial injury
what are risk factors for developing arterial thromboses?
stasis, venous injury, hypercoagulability
what is post-op DVT treatment (1st, 2nd, 3rd lines)?
1st: warfarin for 6 months. 2nd: warfarin for 1 yr. 3rd or significant PE: warfarin for lifetime
when are greenfield filters given?
- contraindications to anticoagulation, 2. documented PE while on anticoagulation, 3. free-floating IVC, ilio-femoral, or deep femoral DVT, 4. recent pulm embolectomy
when can temporary IVC filters be given?
for pts at high risk for DVT (head injury on prolonged bed rest)
are thrombolyics proven for treatment of PE?
no
if pt is in shock from PE despite massive inotropes and pressors, what do you do?
go to OR; otherwise give heparin or suction catheter-based intervention
where do most PEs arise?
ilio-femoral region
what are the procoagulant agents (anti-fibrinolytics)?
E-aminocaproic acid (Amicar)
what are the anticoagulation agents?
(warfarin, SCDs, heparin, LMWH, argatroban, bivalirudin, hirudin, ancrod
how does warfarin work?
prevents vitamin K-dependent decarboxylation of glutamic residues on vitamin K-dependent factors
how do SCDs cause anticoagulation?
improves venous return, induces fibrinolysis w compression (release of tPA from endothelium)
how is heparin reversed?
protamine
how does protamine work?
binds heparin
what should PTT be when treating w heparin?
60-90 seconds. (mnemonic is half life heparin 60-90 min)
how is heparin cleared?
reticuloendothelial system
what is the reticuloendothelial system?
mononuclear phagocyte system
what are the risks of taking heparin for a long time?
osteoporosis, alopecia
can heparin be used during pregnancy? warfarin?
heparin doesn’t cross placental barrier, warfarin does
what does protamine cross react with?
NPH insulin
what does cross reaction of protamin and NPH insulin give you?
protamine reaction (hypotension, brady, decreased heart function)
what are examples of LMWH?
enoxaparin, fondaparinux
how does LMWH work? what are the advantages?
LMWH binds and activates AT-III, increases neutralization of JUST Xa and thrombin–> NOT reversed w protamine. advantage is lower risk of HIT (compared to unfractionated heparin)
how does argatroban work?
it is a reversible direct thrombin inhibitor
how is argatroban metabolized?
liver
what is argatroban half life?
50 minutes
when is argatroban used?
in pts with HITT
how does bivalirudin work?
reversible direct thrombin inhibitor.
how is bivalirudin metabolized?
proteinase enzymes in blood
what is bivalirudin’s half life?
25 minutes
where does hirudin come from?
leeches
how does hirudin work?
irreversible direct thrombin inhibitor, most potent direct inhibitor of thrombin
what is the risk of hirudin?
high risk for bleeding complications
what is ancrod and how does it work?
malayan pit viper venom; stimulates tPA release
of argatroban, bivalirudin, hirudin, which ones are reversible and which are irreversible direct thrombin inhibitors?
argatroban and bivalirudin are reversible
what are the thrombolytics?
streptokinase, urokinase, and tPA
what do thrombolytics do?
activate plasminogen
what is the treatment for thrombolytic overdose?
E-aminocaproic acid (Amicar)
what are the minor contraindications for thrombolytic use?
minor surgery, recent CPR, AF w MV dz, bacterial endocarditis, hemostatic defects (ie renal or liver disease), diabetic hemorrhagic retinopathy, pregnancy
what are the major contraindications for thrombolytic use?
recent (<10d) surgery, organ biopsy, obstetric delivery, left heart thrombus, active PUD, recent major trauma, uncontrolled HTN, recent eye surgery
what are the absolute contraindications for thrombolytic use?
active internal bleed, recent CVA or neurosurgery (<3 mo), intracranial pathology, recent GI bleed
what should hct and platelets be before surgery in pts with PCV?
hct <400 before surgery
which types of VWD are autosomal dominant and which are autosomal recessive?
I and II are autosomal dominant, III is autosomal recessive
what are the initial events to thrombus formation?
- platelet adhesion
- shape change
- granule release
- recruitment
- hemostatic plug
- collagen exposure
what do you need to follow when using thrombolytics? how high should it be?
fibrinogen levels should be >100. if <100, associated with risk and severity of bleeding
how does heparin work?
binds and activates anti-thrombin III (1000x more activity)
how does ASA work?
inhibits cyclooxygenase (COX) in platelets and decreases TXA2.
can platelets resynthesize COX?
no. they dont have DNA
what is the treatment for factor V leiden?
heparin, warfarin
what is the treatment for protein C or S deficiency?
heparin, warfarin
how does factor V leiden mutation cause problems?
causes resistance to activated protein C; the defect is on factor V.
what is the most common congenital hypercoagulability disorder?
factor V leiden mutation (30% of spontaneous venous thromboses)
how high should platelets be before and after surgery?
> 50,000 before, >20,000 after
when does coumadin need to stop before surgery? what do you need to consider in pts who require coumadin during this time?
stop 7 days before surgery, consider bridge to heparin
if a pt has epistaxis, what diseases are most likely?
vWF deficiency and platelet disorders
what is a consider in prostate surgery in terms of bleeding?
can release urokinase, which activates plasminogen –> thrombolysis.
how are most patients with bleeding disorders revealed?
tooth extraction or tonsillectomy
what is treatment for plavix overdose?
platelets
what ist he treatment for prothrombin gene defect G202010 A?
heparin, warfarin
what is the treatment for hyperhomocysteinemia?
folate and b12
what causes APLAS?
antibiodies to cardiolipin and lupus anticoagulant (phospholipids)
what is the most common factor causing acquired hypercoagulability?
tobacco
what is treatment for APLAS?
heparin, warfarin
what are causes of acquired hypercoagulability?
tobacco, malignancy, inflammatory states, inflammatory bowel dz, infections, oral contraceptives, pregnancy, RA, post-op, myeloproliferative disorders
how do you diagnose APLAS?
prolonged PTT (corrected with FFP), russell viper venom time, false pos RPR test for syphilis
how does cardiopulmonary bypass cause hypercoagulation? what can you do to prevent?
factor XII (hageman factor) is activated. Heparin prevents it.
what is the treatment for dysfibrinogenemia, dysplasminogenemia?
heparin, warfarin
how does polycythemia vera cause cause clots? what is treatment?
defect in platelet fxn, can get thrombosis. Rx: phlebotomy, ASA
what is the treatment for antithrombin III deficiency?
heparin does not work in these pts. Rx: recombinant AT-III concentrate or FFP (highest concentraiton of AT-III) followed by heparin, then warfarin
what happens to coags in APLAS?
prolonged PTT…but they are hypercoagulable
do all pts with APLAS have SLE?
no
what is special about factor X?
convergence point between intrinsic and extrinsic and is common for both paths.
what is the treatment for prostate surgery bleeding?
E-aminocaproic acid (amicar)
what is the prothrombin complex?
tissue factor (injured tissues) + factor VII –> activate X, then add V –> convert prothrombin to thrombin –> thrombin then converts fibrinogen to fibrin
what does XIII do?
helps crosslink fibrin.
what is heparin half life?
60-90 minutes
what are the thrombolytic agents?
streptokinase, urokinase, tPA
when does clopidogrel (plavix) need to stop before surgery? how does it work?
stop 7d before surgery. it is an ADP receptor antagonist.
