Coagulation And Platelet Disorders Flashcards
1
Q
Complex interaction b/t progocagulant and anticoagulant factors, mediated by vascular endothelial cells
A
Normal hemostasis
Localized fibrin/platelet plug prevents blood loss while keeping clot fro extending beyond injured area
Blood plug and prevention of clotting to non injured sites
2
Q
Major players in coagulation
A
Endothelial cells
Subendothelial matrix
VWF
Platelets
3
Q
Endothelial cells coagulation fxn
A
Secrete small amount of NO, ADPase, and prostacyclin = inhibition and vasodilation
When damaged = production ceases, begin producing procoagant and tissue factor
4
Q
What causes platelet capture and activation
A
Sub-endothelial matrix/TF exposure
This is facilitated by vonWillebrand’s factor
5
Q
VonWillebran’d factor
A
Large molecule synthesized in multimeric strings in EC and megakaryocytes
Circulates in plasma and becomes bound to exposed subE matrix
Loosely adhere platelets at site of injury, causing platelets to slow roll along vessel
factor 8 carrier
6
Q
Binding of vWF causes
A
Binding occurs at the GPIIb/IIIa receptor
Conformational change of the receptor –> ACTIVATED
7
Q
Hormone that mediates platelet suppply
A
Thrombopoeetin
From liver, kidney, muscle, BM
8
Q
Platelet activation causes:
A
Recruitment of addition platelets (via thromboxane A2)
Vasoconstriction (thromboxane A2 and serotonin)
Fibrin formation
9
Q
Imp. Molecules in the platelet membrane (3)
A
- Glycoprotein IIb/IIIa (binds platelets, fibrinogen, vWF)
- Phospholipids
- Absorbed coagulation factors
10
Q
Granules in platelet cytoplasm contain (3)
A
- Hemostais mediators (fibrinogen, plasminogen, coat factors)
- Vasoconstrictors
- Platelet derived growth factors
11
Q
Minimum req. platelet counts:
Prevention of spontaneous bleeding
A
10-20,0000
12
Q
Minimum req. platelet counts:
Central line insertion
A
20-50,0000
13
Q
Minimum req. platelet counts:
Administration of therapeutic anticoagulant
A
30-50,000
14
Q
Minimum req. platelet counts:
Minor surgery
A
50-80,000
15
Q
Minimum req. platelet counts:
Major surgery
A
80,000-100,000
16
Q
Major site of coagulation factor synthesis
A
Liver
Some of the coagulation factors and natural anticoagulants are vitamin K dependent
17
Q
Limiters of clot formation
A
Anti-thrombin III
Protein C and S
18
Q
Anti-platelet agents
5
A
- Aspirin
- NSAIDS
- COX-2 Inhibitors
- Thienopyridines
- GP IIb/IIIa inhibitors
19
Q
Aspirin
A
Permanently inhibits COX-1 for life of platelet
Prevents it from making thromboxane A2 (no platelet accumulation)
20
Q
NSAIDs
A
Reversible and competitive binding to COX-1
Anti platelet effects depend on drug concentration, varies over time
Given 2 hrs after ASA so not to dampen aspirin effect
21
Q
COX-2 Inhibitors
A
Thought to be platelet neutral (only targeting leukocytes)
Decreases production of prostacyclin so can cause stroke, HTN, MI j
22
Q
Thienopyridine
A
Impair platelet aggregation by inhibiting ADP biding to platelets and ADP activation of GP 2b/3a receptor
23
Q
Thienopyridine indications
A
CAD, unstable angina, acute coronary syndrome, acute MI
Clopidogril - TIA, stroke
24
Q
Coagulation medications (5)
A
- Direct thrombin inhibitors
- Heparin
- LMWH
- Xa Inhibitors
- Warfarin/Coumadin
25
Direct thrombin Inhibitors indications
Leprudin and argatroban are sub q/IV for HIT
Pradaxa is for clot prevention, AFib, DVT, PE
26
Heparin
Acceleration of ability of ATIII to inactivate thrombin and clotting factors
No NEW clots are formed
Administered as a drip
Measured with a PTT
27
LMWH
Acceleration of ability of AT III to inhibition activation of X
Less effect on platelets, more stable, Sub Q, no monitoring
But must consider renal clearance
28
Indications of Xa
Prophylaxis of thromboembolism in Afib
DVT/PE
29
Warfarin
Vitamin K antagonist, decreses synthesis of vitamin K dependent clotting factors
Monitored with PT/INR
Dosed with therapeutic middle dose (INR of 2.0-3.0)
Reversed with FFP or Vitamin K injection
30
Arterial problem, which drugs?
Antiplatelet
ASA or theianopyridine
31
Venous problems, which coagulant?
NOACs, Coumadin
32
Small vessel bleeds typically causes
Petechiae
Most often in GI, mucous membranes, skin
Occurs in PLATELET def.
33
Large vessel bleeding typically produces
Purpura and hematomas
Occur in muscles, solid organs, joints
FACTOR issue
34
Labs for blood evaluation (6)
CBC
PT/INR
PTT
Blood smear
Platelet count
Bone marrow biopsy
35
Vascular puppy
Disorders of blood vessels
Caused by structural integrity of blood vessel or by inflammation of vessel
36
Structural integrity problems that might cause vascular purpura
Senile purpura
Steroid induced
Scurvy
Congenital causes
37
Causes of vasculitis
```
Viral infection (EBV, HIV, hepatitis)
Aseptic vasculitis (medicine hypersentivity)
Septic vasculitis
Connective tissue disease (SLE, RA)
Muscular disease
```
38
Causes of thrombocytopenia (3)
1. Splenic sequestration
2. Decreased platelet production
3. Rapid death/utilization
39
Causes of decreased platelet production (5)
1. Medications
2. Nutritional disorders
3. Bone marrow disease
4. Myelodysplasia
5. Congenital dz
40
Medications that decrease platelet production
Cytotoxic or immunosuppressive meds (cancer, autoimmune)
Thiazides, alcohol, BC
41
Myelodysplasia
Replacement of platelet progenitor cells with dysplastic cells
If with fibrosis -- myelofibrosis
42
Splenomegaly and thrombocytopenia
Increased trapping, causes plasma levels of 50-100k
Typically in liver dz, CML, and malignancies with spleen
43
Peripheral planet destruction causes
1. Immune mediated
| 2. Non immune mediated
44
Immune mediated peripheral platelet destruction
Platelet is coated with anti-platelet auto-abs
Then it is cleared from circulation by spleen
Shortens lifespan
45
4 types of quantitative deficient platelets
1. ITP
2. HIT
3. TTP
4. HUS
46
Immune thrombocytopenic purpura
Ig-autoantibodies to platelets (formed alone or 2 to other dz)
Coat platelets, increased trapping, and phagocytosis in red pulp of spleen
Can be pediatric or adult
47
Pediatric ITP
Occurs acutely (following nonspecific viral illness - URI or Gasteroenteritis)
Common in children 1-6, male predominance
Recover spontaneously (steroid IVIG can be used to shorten)
Mostly resmmsion w/o recurrence (can do splenectomy if not gone)
48
Adult ITP
Indisputable onset, unlikely to spontaneously resolve
Likely chronic
MC ink 30-40, 2:1 F:M
Have to rule out meds, diseases, and myelodysplastic dz
49
Adult ITP presentation
Typically not systemically ill
Will NOT look sick
Determine if there is possible hemorrhage
50
Adult ITP diagnosis
Isolated thrombocytopenia (no other abnormal cell lines, < 20 k)
Normal peripheral smear
51
ITP treament
Goal: return platelet count to level high enough to prevent bleeding
NO CURE
Withdrawal of possible causative drug or control underlying dz
Treat w/ corticosteroid
52
Corticosteroid and ITP
Decreases platelet autoantibodies production
Decreases splenic sequestration
Stabilizes vascular endothelium (less bleeding)
Best results if mixed with rituximab
53
Additional ITP trement (2)
IVIG (sometimes with steroids, decreases autoantibodies and macrophage activity)
Splenectomy (good for acute)
54
drug induced immune thrombocytopenia
immune mediated platelet destruction due to Abs produced against a DRUG
Abs cross react with platelet Ags -- platelet is collateral damage
very sudden, but can also be recovered quickly with DQ drug
55
drugs that typically cause drug induced thrombocytopenia
1. quinidine, quinine (not commonly used)
2. ABX 9pcn, sulfa, cephalosporins, vanco
3. anti HTN- thiazide, ACEI
4. cimetidine
5. tegretol, dilantin
5. benzos, halloo, lithium
6. plavix
56
heparin induced thrombocytopenia
similar to drug induced, but catastrophic thrombotic complications
taking heparin, develop immune mediated thrombocytopenia (50-100k)
binding of these auto-abs to platelets also activates them so they clot
57
what is the immune complex actually against in HIT?
IgG anti-Heparin- platelet/factor 4 complex
58
pts more likely to get HIT
serum surgical patients
esp. CPB
platlet counts begin to decline around 5-4 days after initiation
59
how is HIT detected?
HIPA serum assay
specific but not sensitive (if positive confirmed, if negative might still be)
60
HIT treatment
discontinue heparin, never give again
can use DTI or anti-coagulant
61
two major functions of vWF
1. binds to platelets at site of injury
| 2. carries and stabilizes factor 8
62
vWF disease
deficiency or dysfunction of vWF that limited platelet adhesion to vessel wall
causes deficiency of factor 8 --> increased bleeding
63
vWF disease epidemiology
1% of population
M:F are 1:1
greater s/s may occur in women
64
s/s of vWF d
excessive bleeding (heavy periods, gum bleed, easy bruising)
delayed bleeding
worse with ASA
65
diagnosis of vWFd
prolonged PTT (factor 8) normal PT
measure vWF levels directly
66
everyday treatment of vWFd
avoid ASA and limit activities that result in sig. bleeding
FFP is effective but not recommended
anti-fibrinolytic
birth control
67
surgery or sig. bleeding treatment of vWFd
DDAVP
can use Factor VIII concentrate w/ vWF (donated factor 8)
68
DDAVP
given to vWFd patients before surgery
stimulates vWF release from platelets --raises them to the adequate levels
69
anti-fibrinolytics used in vWFd treatment
aminocaproic acid (Amicar)
Tranexamic acid (Listed, Cyklokapron)
70
uremia
renal failure causes platelet dysfunction by an unknown mechanism
71
dilution thrombocytopenia
follows massive blood product transfusion after trauma or surgery
CPB is also damaging (only temporary)
72
hemophilia deficiencies in which factors
```
Factor VIII (A)
Factor IX (B, christmas disease)
```
Factor XI (C)
73
Hemophilia factor level
Severe
<1%
74
Hemophilia factor level
Moderate
1-5%
75
Hemophilia factor level
Mild
5-40%
76
Can women get hemophilia?
Not genetically -- only males.
Can get acquired
77
Hemophilia pathophysiology
No factor 8/9 so unable to produce proper amounts of thrombin
Severe bleeding from even minor injury -- but typically following surgery or trauma, spontaneous
78
Hemophilia bleeding where?
Joints (hemarthrosis)
Deep parts of body (GI, CNS, muscles, GU, pulmonary, cardio)
79
Hemarthrosis
Hallmark of hemophilia
Inflammation of synoveal membrane
Causes permenant joint deformation, severe pain, loss of mobility
80
Hemophilia labs
PTT normal/prolonged
PT normal
Specific factor assays will be very low
81
Hemophilia treatment
Recombinant coagulation plasmid factors
Avoid ASA
82
Acquired hemophilia
Spontaneous development of autoantibody to own clotting factors
Develops hemophilia
Male or female
83
DIC is associated with what conditions
Sepsis (esp. gram - bc endotoxins)
Malignancy
Liver disease
Severe trauma/obstetrics
84
Procoagulant substrate DIC
1. Bacterial lipopolysaccharide
2. Tissue factor (sepsis or trauma)
3. Proteolytic enzymes (cancer or placenta)
85
DIC pathophysiology
Coagulation and fibrinolysis are abnormally and massively activated -- extensive thrombi formation and wide spread fibrinolysis
Reduced perfusion, thrombosis and bleeding (organ damage from acidic state)
86
Arterial clots are where
Superimposed on ruptured arteriosclerotic plaque
Smaller clots
87
Virchows triad
1. Hyper coagulability
2. Stasis
3. Vessel damage
Causes of VENOUS clots
88
Rare disease marked by formation of thrombi in microvasculature
Thrombotic Thrombocytopenic Purpura
Vasculature becomes hostile, rips vessels and clots form
89
TTP is associated with what causes
Estrogens, drugs, pregnancy, infections
Adults 20-50, female predominance
90
TTP cause
Acquired or inherited inability to cleave vWF molecules
Lack of ADAMTS13
Causes increased platelet adhesion and aggregation (w.o. coagulation)
91
5 symptom presentation of TTP
1. Fever (>105)
2. Thrombocytopenia
3. Microangiopathic hemolytic anemia (schistocytes, elevated LDH)
4. Neurological symptoms (wax/wane aphasia, HA, LOC. Seizure)
5. Renal insufficiency (elevated creatinine)
92
TTP treamtnet
Plasmapheresis (replace bad plasma and donor)
Look for resolution of neurological changes, decrease LDH, and restore platelet count to >50k
Can also give steroid, rituximab
CI: platelet transfusions
93
HUS
rare, similar to TTP but less neurological symptoms, more RENAL FAILURE
More likely to present in children
94
HUS etiology
Viral or bacterial infection causing diarrheal illness -
Esp. Shigella or E. coli
Other infection, estrogen, post partum, immunosuppressive treatment
Can also be familial
95
HUS lab picture
Similar to TTP
1. COOMBs neg -- greater hemolytic anemia, schistocyte formation
2. Greater renal failure, proteinuria, hematuria
3. Less thrombocytopenia
96
HUS treatment
DIC may be there
Supportive *fluids and treat infection
Hemodialysis to replace renal function
Can use Solaris
97
Factor V Leiden
MC inherited disorder to cause VTE
Mutation that prevents Factor V from inactivation, so hyper coagulation
```
Heterozygous= 5x increased risk
Homo= 90x risk
```
98
You can have a genetic mutation in natural anticoagulant proteins
Extra clotting occurs
Can result increased loss or turnover leading to deficiency
Can cause hepatic disease, nephrotic syndrome
These are in ATIII, Protein C and S
99
When do you suspect inherited thrombophlebitis
1. Pt has strong family history of DVT/PE (esp. 1st degree relatives)
2. Patients with VTE in odd locations
3. Recurrent VTE (not explained by something else)
100
Patients with inherited thrombophlia shold avoid
Estrogen/progesterone contraceptives
Immobilization
Smoking
Pregnancy
101
Where do venous clots occur
Lower extremities, lg deep veins
Venous ultrasound to detect
102
Venous clots are a ____ issue
FACTOR issue
Treated differently from arterial clot (platelet problem)
103
When do yo do thrombophilia workup?
1. After initial VTE if pt <45 and one relative has VTE
2. Recurrence of VTE w/o risk factors
3. Multiple VTE in unusual spots (portal, mesentaric, cerebral, hepatic veins)
104
If discovered thrombophilia bc of genetic test
No prophylactic treatment or anti-platelet meds given
Avoid risk factors
105
Treament if we discovered bc they clot
1. Longer duration of anticoagulant after DVT/PE
106
Thrombocytosis
Platelet count > 500k
1. Reactive (cytokine driven)
2. Autonomous over production by megakaryocyte
107
Reactive thrombocytosis
Caused by infection, post operative status, malignancy, splenectormy and iron deficiency anemia or acute blood loss
Req. history, treat underlying cause or complications
108
Thrombocytosis symptoms
Vasomotor symptoms (headache, lightheaded Ess., atypical chest pain, visual changes, numbers and tingling in fingers)
Bleeding
Thrombosis
