02 Hematology Flashcards
1
Q
which type of VWD is most severe?
A
III. most severe bleeding
2
Q
where do hemophiliacs tend to bleed?
A
joints.
3
Q
will newborns with hemophilia A bleed at circumcision?
A
No. Factor VIII crosses placenta.
4
Q
what is the best coagulation measurement for liver synthetic function?
A
PT
5
Q
what does prostacyclin do?
A
decreases platelet aggregation and promotes vasodilation
6
Q
what does thromboxane do?
A
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
7
Q
what are coagulation factors?
A
cryoprecipitate, FFP, DDAVP
8
Q
what causes type I vWD? what is the treatment?
A
reduced quantity of vWF, treat with recombinant VIII:vWF, DDAVP, cryo
9
Q
what are PTT and PT in hemophilia A?
A
high PTT, normal PT
10
Q
what do you need to make sure in hemophilia A people before surgery?
A
need VIII 100% pre-op, keep at 80-100% for 10-14d after surgery
11
Q
what INR is contraindication for central line placement, percutaneous needle bx, and eye surgery?
A
INR >1.3
12
Q
what INR is contraindication for surgical procedures?
A
INR > 1.5
13
Q
what are the players in fibrinolysis?
A
tissue plasminogen activator, plasmin, alpha-2 antiplasmin.
14
Q
what causes type III vWD? what is Rx?
A
complete vWF deficiency (rare). Rx is VIII:vWF, cryoppt. (DDAVP doesn’t work)
15
Q
what is active clotting time (ACT) for routine anticoagulation and for cardiopulmonary bypass?
A
150-200 sec for routine, >460 for cardiopulm bypass
16
Q
what does thrombin do?
A
it is the key to coagulation. converts fibrinogen to fibrin and fibrin split products, activates factors V and VIII, activates platelets
17
Q
should you aspirate hemophiliac joint bleeds?
A
no! give ice, keep joint mobile with range of motion, give factor VIII concentrate or cryoppt
18
Q
what test do you do to figure out VWD?
A
ristocetin test (bleeding time)
19
Q
where does thromboxane come from?
A
platelets
20
Q
what are the symptoms of hemophiliacs?
A
epistaxis, ICH, hematuria. treat with recombinant factor VIII or cryo
21
Q
what should PTT be for routine anticoagulation?
A
60-90 sec
22
Q
can PT and PTT be normal in VWD?
A
yes. can be nl or abnl
23
Q
what is the most common cause of surgical bleeding?
A
incomplete hemostasis
24
Q
what is the function of vWF?
A
links GpIb receptor on platelets to collagen
25
what does tissue plasminogen activator do?
it is released from endothelium and converts plasminogen to plasmin
26
where does prostacyclin come from?
endothelium
27
when does FFP take effect and how long does it last?
immediately, lasts 6 hrs
28
what does alpha-2 antiplasmin do?
it is a natural inhibitor of plasmin, released from endothelium
29
what is definition of hemophilia A?
VIII deficiency
30
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)
31
which is the only factor not synthesized in liver?
factor VIII. it's synthesized in the endothelium
32
what does PTT measure?
measures most factors except VII and XIII (does not pick up factor VII deficiency). also measures fibrinogen.
33
what do DDAVP and conjugated estrogens do?
cause release of VIII and vWF from endothelium. similar effect as cryoppt
34
what does plasmin do?
degrades factors V, VIII, fibrinogen, fibrin --> lose platelet plug
35
what does protein S do?
vitamin K dependent, protein C cofactor
36
what does protein C do?
vitamin K dependent. degrades factors V and VIII, degrades fibrinogen
37
what does PT measure?
II, V, VII, X, fibrinogen.
38
what is in FFP?
high levels of coagulation factors, protein C, S, and AT-III
39
what is the normal half life for RBCs, platelets, and PMNs?
RBC: 4 months, platelets 7d, PMNs: 1-2d
40
what is another name for factor II?
prothrombin
41
which factor has the shortest half life?
factor VII
42
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.
43
what factor is missing in hemophilia B?
IX
44
how is hemophilia A transmitted?
sex-linked recessive
45
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
46
how many hours does vitamin K take to have effect?
6hrs
47
what is the most common congenital bleeding disorder?
VWD
48
which proteins in anticoagulation cascade vitamin K dependent?
proteins C and S, II, VII, IX, X
49
what is the most common type of VWD?
Type I (70% of cases), only mild sx
50
which factor is labile, lost activity in stored blood, and who continues to have activity in FFP?
factors V and VIII
51
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.
52
what causes bernard soulier?
Gp1b receptor deficiency on platelets (can't bind collagen). vWF normally links GpIb to collagen. Rx is platelets
53
when does ASA need to stop before surgery?
7 days
54
what are the platelet disorders?
acquired thrombocytopenia, glanzmann's thrombocytopenia, bernard-soulier, uremia
55
how does uremia induce thrombocytopenia? what is the treatment?
inhibits platelet fxn. Rx is hemodialysis (1st), then DDAVP, platelets
56
does LMWH have a decreased risk of HIT?
yes
57
what is PT and PTT in factor VII deficiency?
prolonged PT, normal PTT.
58
what are findings in DIC?
decreased platelets, low fibrinogen, high fibrin split products, high D-dimer, prolonged PT and PTT
59
what are lab findings in pts taking ASA?
prolonged bleeding times
60
what causes acquired thrombocytopenia?
H2 blockers, heparin
61
how is hemophilia B transmitted?
sex linked recessive
62
what is treatment for DIC?
treat underlying cause (eg sepsis)
63
high or low doses of heparin to cause HIT?
can occur with low
64
what is treatment for HIT?
stop heparin, start argatroban (direct thrombin inhibitor) to anticoagulate
65
what are PT and PTT in hemophilia B pts?
prolonged PTT, normal PT. same as hemophilia A.
66
how do you treat hemophilia B?
recombinant factor IX, or FFP
67
what is treatment for factor VII deficiency?
recombinant factor VII concentrate or FFP
68
how does HIT cause thrombocytopenia?
antiplatelet antibodies (IgG PF4 antibody) resulting in platelet destruction, platelet aggregation (thrombosis), forms a white clot.
69
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
70
what are the three initial responses to vascular injury?
vasoconstriction, platelet adhesion, thrombin generation
71
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
72
what does fibrin do?
links platelets together (binds GpIIb/IIIa molecules) to form platelet plug --> hemostasis
73
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
74
what does tissue factor inhibitor do?
inhibits factor x
75
what causes warfarin induced skin necrosis?
when pt placed on coumadin without being heparinized first
76
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.
77
who is especially susceptible to warfarin-induced necrosis?
pts w relative protein C deficiency
78
how do you treat warfarin-induced skin necrosis?
heparin if it occurs. prevent by placing pt on heparin before starting warfarin
79
what are the elements in deveoping venous thromboses? what is it called?
virchow's triad: stasis, endothelial injury, hypercoagulability
80
what are the key elements in development of arterial thrombosis?
endothelial injury
81
what are risk factors for developing arterial thromboses?
stasis, venous injury, hypercoagulability
82
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
83
when are greenfield filters given?
1. contraindications to anticoagulation, 2. documented PE while on anticoagulation, 3. free-floating IVC, ilio-femoral, or deep femoral DVT, 4. recent pulm embolectomy
84
when can temporary IVC filters be given?
for pts at high risk for DVT (head injury on prolonged bed rest)
85
are thrombolyics proven for treatment of PE?
no
86
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
87
where do most PEs arise?
ilio-femoral region
88
what are the procoagulant agents (anti-fibrinolytics)?
E-aminocaproic acid (Amicar)
89
what are the anticoagulation agents?
(warfarin, SCDs, heparin, LMWH, argatroban, bivalirudin, hirudin, ancrod
90
how does warfarin work?
prevents vitamin K-dependent decarboxylation of glutamic residues on vitamin K-dependent factors
91
how do SCDs cause anticoagulation?
improves venous return, induces fibrinolysis w compression (release of tPA from endothelium)
92
how is heparin reversed?
protamine
93
how does protamine work?
binds heparin
94
what should PTT be when treating w heparin?
60-90 seconds. (mnemonic is half life heparin 60-90 min)
95
how is heparin cleared?
reticuloendothelial system
96
what is the reticuloendothelial system?
mononuclear phagocyte system
97
what are the risks of taking heparin for a long time?
osteoporosis, alopecia
98
can heparin be used during pregnancy? warfarin?
heparin doesn't cross placental barrier, warfarin does
99
what does protamine cross react with?
NPH insulin
100
what does cross reaction of protamin and NPH insulin give you?
protamine reaction (hypotension, brady, decreased heart function)
101
what are examples of LMWH?
enoxaparin, fondaparinux
102
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)
103
how does argatroban work?
it is a reversible direct thrombin inhibitor
104
how is argatroban metabolized?
liver
105
what is argatroban half life?
50 minutes
106
when is argatroban used?
in pts with HITT
107
how does bivalirudin work?
reversible direct thrombin inhibitor.
108
how is bivalirudin metabolized?
proteinase enzymes in blood
109
what is bivalirudin's half life?
25 minutes
110
where does hirudin come from?
leeches
111
how does hirudin work?
irreversible direct thrombin inhibitor, most potent direct inhibitor of thrombin
112
what is the risk of hirudin?
high risk for bleeding complications
113
what is ancrod and how does it work?
malayan pit viper venom; stimulates tPA release
114
of argatroban, bivalirudin, hirudin, which ones are reversible and which are irreversible direct thrombin inhibitors?
argatroban and bivalirudin are reversible
115
what are the thrombolytics?
streptokinase, urokinase, and tPA
116
what do thrombolytics do?
activate plasminogen
117
what is the treatment for thrombolytic overdose?
E-aminocaproic acid (Amicar)
118
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
119
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
120
what are the absolute contraindications for thrombolytic use?
active internal bleed, recent CVA or neurosurgery (<3 mo), intracranial pathology, recent GI bleed
121
what should hct and platelets be before surgery in pts with PCV?
hct <400 before surgery
122
which types of VWD are autosomal dominant and which are autosomal recessive?
I and II are autosomal dominant, III is autosomal recessive
123
what are the initial events to thrombus formation?
1. platelet adhesion
2. shape change
3. granule release
4. recruitment
5. hemostatic plug
6. collagen exposure
124
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
125
how does heparin work?
binds and activates anti-thrombin III (1000x more activity)
126
how does ASA work?
inhibits cyclooxygenase (COX) in platelets and decreases TXA2.
127
can platelets resynthesize COX?
no. they dont have DNA
128
what is the treatment for factor V leiden?
heparin, warfarin
129
what is the treatment for protein C or S deficiency?
heparin, warfarin
130
how does factor V leiden mutation cause problems?
causes resistance to activated protein C; the defect is on factor V.
131
what is the most common congenital hypercoagulability disorder?
factor V leiden mutation (30% of spontaneous venous thromboses)
132
how high should platelets be before and after surgery?
>50,000 before, >20,000 after
133
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
134
if a pt has epistaxis, what diseases are most likely?
vWF deficiency and platelet disorders
135
what is a consider in prostate surgery in terms of bleeding?
can release urokinase, which activates plasminogen --> thrombolysis.
136
how are most patients with bleeding disorders revealed?
tooth extraction or tonsillectomy
137
what is treatment for plavix overdose?
platelets
138
what ist he treatment for prothrombin gene defect G202010 A?
heparin, warfarin
139
what is the treatment for hyperhomocysteinemia?
folate and b12
140
what causes APLAS?
antibiodies to cardiolipin and lupus anticoagulant (phospholipids)
141
what is the most common factor causing acquired hypercoagulability?
tobacco
142
what is treatment for APLAS?
heparin, warfarin
143
what are causes of acquired hypercoagulability?
tobacco, malignancy, inflammatory states, inflammatory bowel dz, infections, oral contraceptives, pregnancy, RA, post-op, myeloproliferative disorders
144
how do you diagnose APLAS?
prolonged PTT (corrected with FFP), russell viper venom time, false pos RPR test for syphilis
145
how does cardiopulmonary bypass cause hypercoagulation? what can you do to prevent?
factor XII (hageman factor) is activated. Heparin prevents it.
146
what is the treatment for dysfibrinogenemia, dysplasminogenemia?
heparin, warfarin
147
how does polycythemia vera cause cause clots? what is treatment?
defect in platelet fxn, can get thrombosis. Rx: phlebotomy, ASA
148
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
149
what happens to coags in APLAS?
prolonged PTT...but they are hypercoagulable
150
do all pts with APLAS have SLE?
no
151
what is special about factor X?
convergence point between intrinsic and extrinsic and is common for both paths.
152
what is the treatment for prostate surgery bleeding?
E-aminocaproic acid (amicar)
153
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
154
what does XIII do?
helps crosslink fibrin.
155
what is heparin half life?
60-90 minutes
156
what are the thrombolytic agents?
streptokinase, urokinase, tPA
157
when does clopidogrel (plavix) need to stop before surgery? how does it work?
stop 7d before surgery. it is an ADP receptor antagonist.
