Coagulation Flashcards

1
Q

Amyloidosis - Factor, test

A
X (decreased)
Thrombin time (increased)
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2
Q

Conditions affecting vWF levels

A

Increased: Acute phase reaction, OCPs, pregnancy, neonates
Decreased: Type O blood group

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3
Q

Protein S

A

Carrier of protein C.

In turn 60% bound to C4BP.

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4
Q

Reptilase time

A

Snake venom (Batroxobin) from Bothrops snake&raquo_space; Directly cleaves fibrinogen. Unlike thrombin time, not sensitive to heparin.

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5
Q

Time-dependent prolongation on mixing study

A

fVIII inhibitor

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6
Q

Platelet aggregation - Phases

A

1st phase: ADP release

2nd phase: More ADP release, TXA2 release.

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7
Q

Bernard-Soulier

A

CD42 (Gp1b/V/X)&raquo_space; Macrothrombocytopenia

Impaired aggregation with ristocetin

Decreased response to thrombin-induced aggregation

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8
Q

Glanzmann’s thrombasthenia

A

GPIIb (CD41) / IIIa (CD61) abnormality. Normal platelet count.

No aggregation except with ristocetin.

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9
Q

Alpha-granule deficiencies

A
Gray platelet (retain P-selectin)
Quebec platelet (excess u-PA degrades granule)
Paris-Trousseau
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10
Q

Dense-granule deficiencies

A

Chediak-Higashi
Wiskott-Aldrich
Hermansky-Pudlak

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11
Q

Storage pool deficiencies - Testing

A

No second wave on aggregation.

Diminished responses to collagen, arachidonic acid

Note: Both of above also true of aspirin effect

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12
Q

vWD - I, III

A

I - Autosomal dominant. Mild, treatable with DDAVP. Normal multimers.

III - Autosomal recessive. Total absence.

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13
Q

vWD - 2A, 2B, plt-type

A

2A - Most common after I. Very few large multimers. Low activity:antigen ratio. Acquired forms resemble this.

2B - Rare. Exon 28 abnormality&raquo_space; increased Gp1b affinity. Few large multimers. Abnormal RIPA. DDAVP will cause thrombocytopenia.

Plt-type - Gp1b on platelet has higher affinity for vWF. Abnormal RIPA. Fewer multimers. Distinguish with cryo challenge

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14
Q

vWD - 2N, 2M, Plt-type

A

2N - Abnormal fVIII binding site, presents like Hemophilia A.

2M - Decreased Gp1b binding affinity. Very low activity.

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15
Q

Hemophilia A - Congenital & acquired

A

Congenital: Usually intron 22 inversion. XLD, can be seen in women in Turner, homozyg, lyonization

Acquired: Rare, elderly with new bruising

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16
Q

Minor hemophilias

A
Hemophilia C (factor XI, jews, autosomal. No recombinant available)
fIX (anaphylaxis with repletion)
f12 (maybe thrombogenic?)
f7 (maybe also thrombogenic?)
f13
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17
Q

Dysfibrinogenemias

A

Qualitative dysfunction, only partially corrects on mixing due to competitive inhibition.

Diagnose with thrombin time (more sensitive than reptilase time)

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18
Q

Alpha-2 antiplasmin deficiency

A

Test: SLOW euglobulin clot lysis. Normal other coags.

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19
Q

TTP/HUS

A

Normal PT, PTT, fibrinogen, D-dimer. Platelet-rich clots.

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20
Q

Heparin resistance

A

AT-III deficiency

Increased heparin clearance or binding

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21
Q

Homocysteinemia

A

Endothelial dysfunction

Lens dislocation, peripheral neuropathy, maybe low folate?

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22
Q

Hypercoagulability of pregnancy

A

General increase in all factors
Decrease in protein S
APC resistance
Venous stasis

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23
Q

Platelet collagen receptors

A
GPVI (major, plays signaling role, deficiency in Japanese)
Integrin a2b1 (GpIa/IIa)
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24
Q

Wiskott-Aldrich

A

XLD

Thrombocytopenia, eczema, immunodeficiency

Cytoskeletal abnormality, impaired signal transduction

Low IgM, high IgE and IgA

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25
VASP | Cone & Plate analysis
VASP: Flow-based method, gold-standard for P2Y12 inhibitor effect. Cone & Plate: In vitro method studying shear-induced adhesion. Affected by Hct, plt count, meh,.
26
May-Hegglin Chediak-Higashi Fechtner
May-Hegglin - Dohle-like bodies in neutrophils. MYH9 Chediak-Higashi - Peroxidase+ granules in many leukocytes Fechtner - May Hegglin + Alport syndrome
27
Congenital amegakaryocytosis
MPL gene mutation
28
Specimen types in coag testing
Most: Citrated plasma (3.2% NaCit) Flow: Whole blood Plt agg: Platelet rich and poor plasma (still collect in blue top)
29
PFA-100: Patterns
ASA: Col/Epi prolonged, Col/ADP normal Plavix: Variable, both may be prolonged BSS, GT: Both prolonged
30
ITP targets
Usually GpIIb/IIIa or Ib/V/X
31
IIb/IIIa inhibitors
Abciximab (Fab fragments) Tirofiban (nonpeptide) Eptifibatide (oligopeptide)
32
Plavix
``` Blocks P2Y12 (irreversibly) Prodrug, activated by 2C19 ```
33
Scott syndrome
Disorder of flippase Abnormal Annexin V on flow Shortened PT
34
TXA2 metabolites
Metabolized to TxB2, then to 11-dehydroTxB2 in urine.
35
Plt aggregation - Types, agonists
Types: Turbidometric (gold standard), impedance, lumiaggregometry Agonists: Col, ADP, Epi, AA, Thrombin, TRAP, Ristocetin, U44619
36
Aggregometry - Aspirin, plavix
Aspirin: Impaired TXA2 production. No second wave after ADP/Epi agonism. Plavix: No first wave with ADP agonist.
37
Falsely elevated plt count on hematology analyzer
Red cell fragments (schistocytes, AML) Microorganisms
38
NAIT
Usually due to HPA-1a > 4b (Asian) antibodies. Treat with maternal platelets. Ddx: Maternal ITP with placental transfer (mom should be thrombocytopenic)
39
Fonio method
To estimate platelet count, multiply the number of platelets seen on a 1000x field by 20.
40
Plt histogram
Right skew
41
ITP Tx
Steroids, IVIG Second-line: Rituximab, other immunosuppressants
42
PAR-1 | PAI-1
PAR-1 - Thrombin receptor on platelets | PAI-1 - Plasminogen activator inhibitor (serpine antifibrinolytic protein on...endothelium?)
43
Jackass platelet trivia
10^11 produced per day | 7-10d lifespan
44
Clinical presentation of platelet-type and coagulation-type bleeding
Platelet-type: Mucocutaneous bleeding, excessive bleeding from minor trauma Coagulation-type: Deep or delayed bleeding, bruising, hemearthroses
45
TPO agonists
eg Romiplostim, eltrombopag May cause bone marrow fibrosis (reticulin deposition)
46
Weibel-Palade bodies
Contain vWF, P-selectin
47
VitK dependent factors. What conditions affect these?
2, 7, 9, 10, C, S Warfarin, antibiotics, IBD
48
Factor half-lives
fVII - 6hrs (shortest) fVIII - 12hrs fIX - 24hrs fXIII - week (longest)
49
NovoSeven
Activated factor 7, can be used as bypass agent. Very short lived.
50
Factor dosing
fVIII - Bw(kg) x %change, divided by 2. | fIX - Bw(kg) x %change
51
Pharmacogenetics of warfarin
VKORC polymorphisms may confer resistance Metabolized by CYP2C9
52
Early activators of intrinsic pathway
HMWKgen activates fXII which activates pre-kallikrein. HMWKgen deficiency does NOT correct on mixing aPTT.
53
fXIII treatment
Cryoprecipitate | Corifact (recombinant fXIII)
54
Brill-Edwards regression
Relates aPTT to anti-Xa activity (0.3-0.7 goal)
55
Indications for thrombophilia testing
Thrombosis <50yo Unusual thromboses Recurrent thromboses Primary family member with thrombophilia
56
APC resistance Protein C assay (functional) Protein S assay (functional)
APC resistance: Spike APC into patient plasma, look for expected prolongation of clotting Protein C assay: Use protein C activator (not APC itself) Protein S assay: Also spikes APC, looking for expected prolongation of clotting
57
AT3 Testing
Chromogenic reagent is normally generated by thrombin. Add heparin and patient sample (AT). Normally, chromogenic substance should not be generated.
58
Causes of decreased AT3
Liver disease Nephrotic syndrome Thrombosis? IBD? Pregnancy? L-asparaginase
59
APCR elevation
``` Factor V leiden Any inhibitors (LAC, heparin) Factor deficiencies ```
60
DRVVT
Protac snake venom activates protein C. More protein C prolongs clotting time. Used as screening test for LAC.
61
Purpura fulminans
Deficiency of protein C, as seen in DIC, newborns, warfarin without bridging, and homozygous C deficiency.
62
INR calculation | ISI calculation
(PT / geomean) ^ ISI ISI is slope of reference PT means to lot PT means
63
Heparin side effects
Bleeding Osteoclast activation, osteoblast suppression >> osteoporosis
64
Protamine
Arginine rich, positively charged antidote to UFH > LMWH
65
Liver transplant phases
Anhepatic stage: Activation of fibrinolysis, loss of factors >> BLEEDING Postreperfusion: Correction o fibrinolysis, slow replenishment of factors, but plt sequestration Postoperative: HYPERCOAGULABLE
66
Heparin cofactor II
Minor target of heparin (adjunctive to AT3). Inactivates only IIa.
67
Factors produced exclusively in liver, or not in liver at all
Only made in liver: PAI-1, Plasminogen | Not made in liver: vWF,
68
Josso loop
In vivo activation of factor IX by TF-VIIa complex
69
At what dilution would an 8-bethesda inhibitor reduce activity by 75%?
1: 4 - 25% residual *** 1: 8 - 50% residual 1: 16 - 75% residual
70
TFPI | Thrombomodulin
TFPI - Inhibits TF-VIIa complex | Thrombomodulin - Activates protein C, has minor procoagulant and anti-inflammatory functions
71
Germline RUNX1 mutation
Thrombocytopenia, increased risk of AML
72
Chromogenic factor X
For warfarin monitoring of patients with LAC.
73
Activated clotting time (ACT)
Uses whole blood and a contact activator. For very high heparin levels (eg, bypass) Takes >100 sec to result
74
Heparin assay
Titrate heparin using protamine