Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Med Gen Section 3 > Coagulation Disorders > Flashcards

Coagulation Disorders Flashcards

1
Q

What are the parts of primary hemostasis?

A 
vessel injury
platelet adhesion
platelet activation
platelet aggregation
platelet plug
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What kind of disorders are associated with vessel injury?

A

vascular/connective tissue disorders

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What kind of disorders are associated with platelet adhesion, activation, or aggregation?

A

thrombocytopenias (decreased production, increased destruction, abnormal distribution)
platelet function defects (receptor/membrane defects, storage granule defects, inhibition (eg. medications or toxins)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What kinds of disorders are associated with platelet plug?

A

von Willibrand disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How do labs analyze platelets?

A 
electronic detection (not accurate at counts lower than 10,000/mm3 and does not detect macrothrombocytes or platelet clumping)
peripheral blood smear (can see size and morphology)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the three steps of platelet aggregation?

A
  1. adhesion to site of injury at subendothelial vWF/collagen (platelet GP1b IX-V adn GPVI)
  2. Activation (platelet shape change exposes the GPIIb/IIIa receptors and releases thrombin, ADP, TXA3, and 5HT)
  3. Aggregation (follow cross-linking of platelet activated GPIIb/IIIa by fibrinogen or vWF)
  4. propagation of coagulation (activated platelets provide an anionic aminophospholipid rich surface for the assembly of procoagulant enzyme complexes)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

List the names and functions of alpha granules.

A

vWF: major role in blood coagulation
Fibrinogen: binds platelet GPIIb/IIIa to form bridges between platelets
PF4: binds heparin and provides neutralization heparin-like molecules (inhibits local ATIII and enhances coagulation)
Growth Factors: PDGF/TGF-beta1
Coagulation Factors: Factor V
P-selectin: cell adhesion molecule which promotes platelet aggregation through platelet-fibrin and platelet-platelet binding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

List the names and functions of dense granules.

A

ADP/ATP: activates platelets causing recruitment of additional platelets
Serotonin: powerful vasoconstrictor
Calcium: required for binding of fibrinogen to platelet GPIIb/IIIa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are halmarks of thrombocytopenias in general?

A

shortened platelet lifespan
platelet sequestration or pooling
platelet loss or dilution
diminished/impaired platelet production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

List the immune mechanisms of thrombocytopenia.

A 
immune thrombocytopenia
Evan's syndrome/Autoimmune lymphoproliferative syndrome
Neonatal alloimmune thrombocytopenia
Neonatal autoimmune thrombocytopenia
Heparin induced thrombocytopenia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

List the non-immune mechanisms of thrombocytopenia.

A

Disseminated intravascular coagulopathy
Bacterial infections
Thrombotic thrombocytopenia purpura/hemolytic uremic syndrome
Kasabach-Merritt syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe immune thrombocytopenia.

A

most common thrombocytopenia in children
present when platelet counts <10,000
can be associated with recent bacterial infection
children present with mostly skin findings due to mucosal bleeding and are otherwise healthy
development of severe hemorrhage is rare

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the mechanism of immune thrombocytopenia?

A

platelet surface looks abnormal –> autoantibody production –> increased platelet removal –> decreased platelet production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How can you tell which hereditary thrombocytopenia a person has by looking at the size of their platelets?

A

Small: WAS
Normal: TAR, CAMT
Large/Giant: Bernard-Soulier, MYH9

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe Wiskott-Aldrich Syndrome.

A

XLR mutation of WASP gene (Xp11.23) resulting in defects in surface of glycoprotein CD43 (actin binding signalign protein)
variable thrombocytopenia with small platelets and poor function
triad of thrombocytopenia, eczema, and frequent infections
associated with defects in T and B cells and inability to form antibodies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What complications are associated with Wiskott-Aldrich Syndrome?

A

hemorrhage (internal and mucosal)
infection (post splenectomy sepsis, viral pneumonia)
autoimmune disorders
malignancy (ALL, lymphomas)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How is Wiskott-Aldrich Syndrome treated?

A

supportive management of eczema and infection
splenectomy usually beneficial
stem cell transplantation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Describe MYH9 related disorders.

A

AD macrothrombocytopenias
mutations involving the MYH9 gene which encodes for non-muscle myosin heavy chain 11A on chromosome 22q13.1
includes leukocytes that present as Dohle bodies
associated with renal failure, sensorineural hearing loss, and cataracts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Describe TAR syndrome.

A

Thrombocytopenia Absent Radii
complex inheritance of a mutation to the RBM8A gene located at 1q21.1 which provides instructions for making a protein called RNA-binding motif protein 8A
presents with radial anomalies with NORMAL thumbs
50% associated with gastritis and cow’s milk intolerance
diminished or absent megakaryocytes with elevated TPO levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How is TAR syndrome treated?

A

platelet transfusions (sometimes daily) will increase platelet count to normal after about 12-14 months

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Describe CAMT.

A

Congenital Amegakaryocyte Thrombocytopenia
AR mutation involving the gene for the TPO receptor c-MLP located at 1p34.2
neonatal platelet count is normally below 20,000/mm3 with some degree of bleeding in most children
progression to aplastic anemia within 5 years
about 50% have additional anomalies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How is CAMT treated?

A

supportive care with platelet transfusions

stem cell transplant is curative

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Describe Glanzmann’s Thrombocytopenia.

A

AR defect in the alphaIIbbeta3 integrin resulting in deficiency or absence of platelet membrane fibrinogen receptor GPIIb/IIIa
severe mucocutaneous bleeding starting in infancy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How is Glanzmann’s Thrombocytopenia diagnosed and what is the treatment?

A

diagnosed by combination of clinical findings, platelet aggregation, and flow cytometry showing:
absent platelet aggregation in response to ADP, epinephrine, and collagen
normal risocetin induced platelet aggregation
managed with platelet infusions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Describe Bernard-Soulier syndrome.

A

AR mutation resulting in abnormal or absent surface receptors for von Wilibran Factor
mucocutaneous bleeding starting in infancy
mild to moderate macrothrombocytopenia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

How is Bernard-Soulier syndrome diagnosed?

A

combination of clinical findings, platelet aggregation, and flow cytometry indicating:
normal response to ADP, adrenaline, and collagen
abnormal response to ristocetin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Describe alpha granule storage pool defects.

A

seen on light microscopy
contain fibrinogen, PDGF, vWF, PF4, Protein S, Factor V, Fibronectin, thrombospondin, beta-thromboglobulin
absent in grey platelet syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Describe dense granule storage pool defects.

A

seen on electron microscopy
contains serotonin, calcium, ATP, and ADP
absent in dense granule storage disease, Hermansky-Puldak syndrome, and Chediak-Higashi

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What is von Wilibrand Factor?

A

platelet binding protein that carries Factor VIII
increased by physiologic stress, DDAVP, estrogen, and pregnancy
acute phase reactant

30
Q

Why do you need to test vWF multiple times to diagnose a defect?

A

because it has many pathways that increase it and can give you false results, so you need to do multiple tests to see its trends over time

31
Q

What are the disease types associated with von Wilibrand Factor?

A 
Type 1 (heterozygous defect with reduced production of normal vWF)
Type 2A (multimerization defect with absent large/intermediate size multimers)
Type 2B (gain of function mutation in vWF resulting in platelets that are too adherent and attach to large multimers instead of letting them circle)
Type 2M (loss of function where vWF doesn't bind well to platelets- opposite of 2B)
Type 2N (loss of vWF binding function to FVIII- normally compound heterozygotes with Type1)
Type 3 (absence of vWF production resulting in patients that bleed like hemophiliacs)
32
Q

Which von Wilibrand Factor disease types are Autosomal Dominant?

A

all but Type 3

33
Q

What screening tests are available to diagnose von Wilibrand Factor diseases?

A

no screen can rule out any of these diseases
PT will always be normal
PTT is only abnormal if FVIII is low
bleeding time and PFA-100 are not sufficiently sensitive

34
Q

What diagnostic testing is available for von Wilibrand Factor diseases?

A 
vWF antigen (vWF:Ag)- immunologic test for presence of vWF in plasma (does not show function)
Factor VIII activity- assesses FVIII activity in blood and binding to vWF
Ristocetin cofactor activity (vWF:Rcof)- platelet aggregation based test assessing vWF platelet binding function
vWF multimer analysis- assesses molecular structure of vWF on an agarose gel (normally present in variety of sizes- low, high, and intermediate molecular weight multimers)
35
Q

How does blood type affect vWF levels?

A

all blood types have different vWF concentrations (Type AB>Type B>Type A> Type O)
these concentrations decrease with vWF diseases so that normal Type O is about the same concentration as diseased Type AB

36
Q

What factor defects most commonly result in the hemophelias?

A

FVIII and FIX

37
Q

List they types of defects of secondary hemostasis.

A

inherited factor deficiencies
acquired factor deficiency
acquired inhibitory antibodies

38
Q

Name the inherited factor deficiencies.

A

Hemophilia A and B

rare: fibrinogen, FV, FVII, FX, FXI, FXIII deficiencies

39
Q

What are the causes of acquired factor deficiencies?

A 
Vitamin K deficiency (FII, FVII, FIX, and FX plus Protein C and S)
liver dysfunction (all but FVIII made here)
DIC (consumption of factors)
40
Q

How are disorders of the coagulation cascade screened for?

A 
PTT is almost always prolonged (some mild hemophilia patients will have normal as will some genotypes due to the way FVIII/FIX interacts with phospholipids and reagents)
Factor Assays (measure specific factor activity levels)
Genetic Assays (genotyping to determine specific molecular defects)
41
Q

What is Hemophilia A?

A

XL R deficiency due to mutations on Xq28

results in spontaneous bleeding, hemarthroses, and deep tissue bleeding

42
Q

What is Hemophilia B?

A

XL R deficiency due to mutations on Xq27.1
results in spontaneous bleeding, hemarthroses, and deep tissue bleeding
carriers (normally female) never have bleeding issues and may not know they carry if their family have less severe versions

43
Q

How are Hemophilias classified?

A

by factor activity
<1%= severe (will most likely develop antibodies to platelet replacement therapy)
1-5%= moderate (trauma induced spontaneous bleeding)
>5%= mild (rarely have spontaneous bleed but problems with surgery)

44
Q

Is prenatal diagnosis possible for hemophilias?

A

factor levels are not reliable enough for prenatal testing because FIX levels are physiologically low in all fetuses and FVIII levels can be falsely elevated
testing is easiest when genetic information is available about the family to test for mutations

45
Q

How are carriers of hemophilias diagnosed?

A

heterozigous women can be symptomatic, but their factor levels fall in the mild range (so you could diagnose by factor levels but you would also need to rule out vWF disease)
most reliable way is to diagnose through genotyping

46
Q

What clinical factors are associated with Factor XIII deficiency?

A

delayed umbilical cord separation
wounds that re-bleed
unstable fibrin clots
normal coagulation studies

47
Q

How is Factor XIII deficiency treated?

A

FFP or cryoprecipitate

human plasma derived FXIII concentrate (Fibrogammin D) every 4-6 weeks

48
Q

List the natural coagulation inhibitors.

A

antithrombin (most potent- acts at thrombin and FXa)
tissue factor pathway inhibitor (acts of TF in the VII –> VIIa reaction)
Protein C and S (act at FV and FVIII)
other less common ones

49
Q

What innate factors influence the production or activity of anticoagulant factors?

A 
decreased at birth (results in 1st year of life need to be interpreted against age associated normal ranges; AT and PS reach adult levels by 6-12 months while PC stays low until adolescence)
liver disease (liver produces coagulation proteins, so diseased livers create a deficiency and/or decrease clearance of activated factors, increasing risk for coagulopathy/thrombosis)
inflammation increases FVIII activity
50
Q

What is thrombophilia?

A

the predisposition to develop thrombosis including:
venous thrombotic events (VTE) such as DVT, PE, cerebral sinovenous thrombosis (CSVT), renal vein thrombosis, potral vein thrombosis, or mesenteric
OR
arterial events such as arterial ischemic stroke or catheter related events

51
Q

List the most common inherited thrombophilias.

A 
Antithrombin deficiency
Protein C deficiency
Protein S deficiency
Factor V Leiden mutation
Prothrombin G20210A mutation
52
Q

Describe the properties of Antithrombin.

A

made in the liver
neutralizes thrombin (IIa), Xa, and IXa
heparin potentiates activity
2 binding sites (heparin binding site and reactive center)

53
Q

What are acquired causes of Antithrombin deficiency.

A 
heparin (increases clearance)
DIC
hurns
liver disease (decreases synthesis)
sepsis
trauma
nephrotic syndrome (protein loss)
54
Q

What is AT-III deficinecy?

A

Antithrombin deficiency (Type 1 or 2)
autosomal dominant
results in thrombotic events (PE, DVT, or mesenteric mostly)
40% of events are spontaneous with increased recurrence rate
homozygotes result in fetal demise

55
Q

Describe Protein C.

A

vitamin K dependent protein produced in the liver

requires activation by thrombin/thrombomodulin complex

56
Q

What is Protein C deficiency?

A

AD (or rare AR form)
varies with age (20-40% as neonate with normalization in adolescence)
majority of events will be venous thrombotic events (illiofemoral veins, mesenteric veins, PE, CVST, superficial thrombophlebitis)
possible association with arterial stroke
70% spontaneous thrombosis
high risk of recurrence

57
Q

What are acquired causes of Protein C deficiency?

A

liver disease (decreased production)
DIC (consumption)
sepsis (meningococcemia)
uremia (decreased activity)

58
Q

How can Protein C deficiency be tested?

A 
antigen tests (immunologic based ELISA, Radioimmunoassays/electroimmunoassays)
functional tests (snake venom activated Protein C and activity of APC measured by clotting assay or chromogenic substrate)
NOTE: Factor V leiden mutants may have artificially low PC/PS activity
59
Q

What is severe PC deficiency in neonates?

A

homozygous deficiency or double heterozygote state
presents with purpura fulminans, opthalmologic or renal injury, neural
treated with anticoagulation (heparin and warfarin) lifelong plus aggressive Protein C replacement
case reports of liver transplant

60
Q

Describe Protein S.

A

Vitamin K dependent protein produced in the liver, endothelial cells, platelets, and brain cells
40% free protein which is active, the rest is bound to C4b-binding protein and is inactive (binding is increased during inflammatory state)

61
Q

What are the acquired causes of Protein S deficiency?

A 
estrogen (OPCs and pregnancy)
DIC
liver disease
acute thrombosis
inflammatory states (decreased free PS)
62
Q

What is Protein S deficiency?

A

Types 1-3
mostly result in venous thrombotic events (DVT, PE, superficial thrombophlebitis, mesenteric veins, CSVT, axillary vein)
50% spontaneous events
high risk of recurrence

63
Q

How is Protein S deficiency screened for?

A

ELISA testing for total and free PS antigens
indirect functional assays based on gene ratios of APC
NOTE: FV leiden mutants may have artificially low PC/PS activity

64
Q

How do medications impact levels of natural anticoagulant proteins?

A

heparin decreases AT levels
warfarin decreases PC and PS levels
oral contraceptives decrease PS and increase activated PC resistance

65
Q

Describe Factor V Leiden.

A

accounts for most of the activated protein resistance (APCR) which slows inactivation by active PC

66
Q

What is Factor V Leiden mutation?

A

Arg506Gln
results in primary venous disease and pregnancy complications (arterial complications debated)
low risk of recurrence in heterozygous state

67
Q

What is Prothrombin G20210A?

A

increases prothrombin biosynthesis
increases risk of venous thrombotic event
possible increase of arterial stroke in children
possible increase risk of recurrence in children

68
Q

Name the types of anticoagulants.

A

Vitamin K Antagonists
Direct Agents
Indirect Agents

69
Q

Describe Vitamin K antagonists.

A

block Factors II, VII, IX, and X as well as Proteins C and S

Eg. Warfarin

70
Q

List the direct agent anticoagulants.

A

Block Xa: Rivaroxaban, Apixaban

Block IIa: Argatroban, Lepirudin, Bivalrudin, Dabigatran

71
Q

List the indirect agent anticoagulants.

A

Block Xa: Fondaparinax
Blocks IIa: UFH
Blocks both: LMWH

72
Q

Who should be screened for thrombophilias according to the guidelines?

A

patients with thrombosis younger than 50 years old, unusual sites, recurrent events, 1st event, and family history

Med Gen Section 3 (13 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions