Bleeding, thrombotic, and Fibrolytic Disorders Flashcards
(74 cards)
1
Q
What are the platelet disorders?
A
- immune thrombocytopenia
- thrombotic thrombocytopenia
- hemolytic uremic syndrome
- henoch-schonelin purpura
2
Q
If you see petechia and purpura what are you thinking the underlying cause is?
A
-PLATELETS!!!! its bleeding underneath the skin, these should not blanch.
3
Q
Immune Thrombocytopenia (ITP):
- etiology- primary/secondary
- what is happening in ITP?
- what age does this occur in?
A
Primary
- usually idiopathic
Secondary
- autoimmune disorders (lupus)
- medications (sulfonamides, thiazides, heparin)
- viral infections (HIV, Hep C)
- in children can be provoked by viral illness
Whats happening?
-pathologic abys bind to platelets resulting in accelerated platelet clearance.
-commonly occurs transiently in childhood, may be chronic in adults and more common in females.
4
Q
Decreased platelets from immune response=???
A
-think thrombocytopenia!!!!!
5
Q
ITP is an immune response in which…? (whats happening)
-quick and dirty explanation
A
-abys bind to platelets resulting in their premature destruction and inadequate production of platelets.
- increased endogenous TPO clearance results in reduced levels of platelets.
- megakaryocytes may be damaged by abys, making them less productive
- suboptimal platelet production results from damaged megakaryocytes and reduced TPO levels
Quick and Dirty: ABY bind to platelet»> platelet destruction
6
Q
Signs and symptoms of ITP
A
- mucocutaneous bleeding (blood blister in mouth)
- petechiae, purpura
- spontaneous bruising
- nosebleeds
- gingival bleeding
- retinal hemorrhage
- excessive retinal bleeding
- melena, hematuria
7
Q
Dx of ITP includes the following…
A
- thrombocytopenia
- normal RBC morphology
- prolonged bleeding time (this means its just a platelet problem)
- +/- anemia
- PT/PTT are normal
- Bone marrow bx
- -normal or increased number of megakaryocytes
*this is a dx of exclusion
8
Q
Tx of ITP
A
- treat w/ prednisone +/- IVIG(only give if no response to steroids within few days) for those w/ symptomatic bleeding or very low platelets.
- splenectomy
- Treat if platelet counts are less than 20-30,000or if significant bleeding
- Prednisone oral: 2-10days
- Dexamethasone: 4day/mo for 6mo.
-May give platelet transfusion if needed. (only give if you need to stop bleeding RIGHT NOW!)
9
Q
Options for failure to respond to oral steroids:
A
- IVIG or anti-D immune globulin
- Rituximab (aby againts CD20)
- thrombopoietin receptor agonist
- splenectomy
- BM transplant or chemo in severe case
10
Q
Thrombotic Thrombocytopenic Purpura (TTP) ?
- what is this?
- quick and dirty explanation
A
- disorder of inapproriate platelet aggregation leading to destruction of RBC and platelet consumption
- make abys against ADAMTS-13 which is responsible for cleaving large vWF molecules into smaller pieces.
Large vonwillibrans molecules are pro-thrombotic. If we dont have ADAMTS-13 cleaving this into smaller pieces we will clot easier and more often (inappropriately)
*emboli shear force on RBC leads to destruction (in terminal vessels and get lodged in kidney and brain)
Quick and Dirty: ABY bind to ADAMST-13»large vWF»clot»RBC destruction and platelet consumption
11
Q
What is TTP characterized by?
A
- thrombocytopenia
- hemolytic anemia
- inapprorpiate platelet aggregation and formation of fibrin.
12
Q
Primary and Secondary Causes of TTP?
A
- Primmary: autoimmune
- Secondary:
- -cancer
- -BM tx
- -Pregnancy
- -Meds: acyclovir, clopidogrel
- HIV
13
Q
What are the 5 main characteristics of TTP?
Which are required for dx? (these will be starred)
A
- Thrombocytopenia*
- Microangiopathic hemolytic anemia*
- Neurologic sx
- kidney failure (dont have to have this but may show up later in disease course)
- fever
14
Q
Sx of TTP?
A
Sx caused by secondary effects of underlying microvascular clotting disorder:
febrile
pallor
malaise
diarrhea
thrombocytopenia = bleeding, bruising
petechiae, purpura
-microvascular clotting leading to organ damage= kidney failure (high creatinine, high BUN, low urine output, edema, blood in urine(RBC casts)),
neurologic sx (HA, diff speech, seizure, transient paralysis, coma, confusion)
15
Q
What will you see in peripheral blood smear of microangiopathic hemolytic anemia?
A
-schistocytes (helmet cells) and low platelets
16
Q
What are some lab abnormalities seen in TTP?
A
- elevated indirect bilrubin
- decreased serum haptoglobin ( free heme binds to haptoglobin; this is why its low)
- microangiopathic hemolytic anemia
- severely elevated LDH
- thrombocytopenia
- marked anemia
- reticulocytosis
17
Q
Thrombocytopenic purpura Tx
A
-plasma exchange (plasmapheresis)
*** do NOT give platelet transfusion, they ‘FUEL THE FIRE’
18
Q
Hemolytic Uremic Syndrome Causes
A
Most commonly it is secondary to -E. Coli 0157:H7
But may be caused by,
- Streptococcus pneumonia
- shigella dysenteriae*
- chemo drugs
- anti-platelet medications
- HIV
- pregnancy
- genetics
19
Q
HUS pathophysiology
A
HUS is caused by endothelial damage secondary to bacterial toxins:
-endothelial damage leads to:
–leukocyte activiation
–platelet activation
–inflammation
–multiple thromboses
resulting in RBC destruction d/c shear forces in the vessel leading to hemolytic anemia.
20
Q
What are the three (TRIAD) things you need to have to be dx w/ HUS?
A
- microangiopathic hemolytic anemia
- acute kidney injury and renal failure
- thrombocytopenia (platelets low becaus they are being used up and cannot be replaced fast enough)
21
Q
What is the main difference between TTP andd HUS?
A
-both have hemolytic anemia but in HUS the kidneys are non-functional and TTP has more neurological sx.
22
Q
HUS signs and symptoms
A
- recent or current bloody diarrhea
- abd pain
- decreased urine output
- hematuria
- renal failure
- hypertension
- neurologic changes
- edema
*same as TTP but with RENAL FAILURE!
23
Q
Tx of HUS?
A
- general tx is supportive
- transfuse RBC and platelets
- dialysis of symptomatic uremia
- nutritional and electrolyte support
- if thought to be secondary to an autoimmune process may be consider plasma exchange.
24
Q
Four major sx associate with Honoch-Schonelin Purpura (HSP)
A
- palpable purpura
- athritis/arthralgias
- abd pain
- renal disease
25
HSP
-cause?
-what age group is affected?
-
- just a vasculititis, no probs bleeding or platelets, triggered by streptococcal upper resp. infection.
- 90% of cases in 3-15years
26
Tx of HSP?
- treatment is supportive
- NSAIDS or glulcocorticoids
- usually just clears but you need to continue to monitor them for renal failure from IgA deposition.
27
HSP work up includes..?
- biopsy of skin lesions*
- CBC
- CMP
- urinalysis (may show hematuria +/- rbc casts (clots formed in rental tubule being passed out of body)
28
What are the bleeding disorders?
- Hemophilia
- VonWillebrands Disease
- Disseminated intravascular coagulation
29
How do you get hemophilia?
What is the most common type of Hemophilia?
- its genetic, x-linked recessive trait in men. women may be carriers
- Hemophilia A
30
Deficiency of what factor will result in hemophilia A? Hemophilia B? Hemophilia C?
- Factor VIII deficiency
- Factor IX deficiency (Christmas disease)
- Factor XI deficiency
31
Characteristic bleeding in hemophilia?
spontaneous hemarthrosis, but other common sites of bleeding are:
Joints: knees, ankles, elbows
Skin, muscle
GU, GI
32
What is hemophilia?
deficiency of coagulation factors, these differ between types A (VII), B (IX), and C(XI).
33
Tx of Hemophilia?
-lifelong replacement of deficient clotting factor, usually 3x/week.
- avoid aspirin
- cryoprecipitate
- DDAVP (stimulates vonwillebrands factor)
34
What do you need for diagnosis?
- PTT is prolonged
- PT, bleeding time, platelets, vonWillebrand factor are normal.
- CONFIRMED by decreased levels of VIII, IX, or XI
35
Do Hemophiliacs bleed longer, bleed more quickly, or have a shortened lifespan?
-Bleed longer.
36
Functions of vonWillebrand factor?
- binds platelets to form the initial platelet plug
| - binds w/ factor VIII to prolong its half-life.
37
How do you get vonWillebrands disease?
-genetics! its autosomal dominant affecting both sexes equally.
38
What is the most common INHERITED bleeding disorder?
-vonWillebrands type 1.
39
What are the types of vonWillebrand disease?
-Type 1: quantitatiev abnormality of vWF, vWF functions normally they just dont have enough.
Type 2: qualitative abnormality, have enough vWF, its just NOT functional. Doesnt bind the way its supposed to.
Type 3: rare, undetectable levels of vWF and severe bleeding in infancy and childhood.
40
Sx of vonWIllebrands diseaes
- easy bruising
- skin bleeding
- prolonged bleeding from mucosal surfaces
- asymptomatic
41
dx of vonWillebrands clues from personal and family hx
- nosebleeds >10mins in childhood
- lifelong easy bruising
- bleeding following dental extractions/surgery
- heavy menstrual bleeding or post partum
42
Lab findings in vonWillebrands
-Plasma vWF antigen (serum concentration of vWF)
- Plasma vWF activity determined by:
- -vWF:Rco and vWF collagen
-Factor VIII activity
- Normal PT
- PTT normal or prolonged depending on the factor VIII activity
43
Tx of vWF:
Type 1
Type 2
Type 3
Minor Major
1: DDVAP, DDAVP vWF conc.
2. DDAVP vWf conc., vWF conc
3. vWF conc., vWF conc.
44
Why dont you give DDAVP to pts w/ Type 3 vonwillebrands factor?
-you dont give DDAVP because they dont make any vWF. its purpose is to activate vWF but they dont make any vWF so it doesnt do any good.
45
What is Disseminated Intravascular Coagulation? Explain what happens in "living room language"
simultaneous hemorrhage and thrombosis at the same time.
What happens:
- massive release of tissue factor stimulated by injury.
- tissue factor set the coagulation system in place
- clotting occurs
- clotting factors and inhibitors are all consumed
- clots further trap circulating platelets leading to ischemia
* **at the same time:
- excess thrombin activates plasmin resulting in fibrinolysis. The breakdown of clots= fibrin degredation products which have further anticoagulant properties
*plasmin also activates the complement and kinin system=shock
46
Causes of DIC
- Cancer
- Obstetric Complications
- Sepsis
- Massive tissue injury (trauma, burns, hyperthermia)
- snake bite
47
Where do all of the clots lodge in DIC?
-in the periphery, commone to have ischemia in handds and feet, capillaries of the skin.
May see petechia, purpura, gangrene, renal and liver failure
48
Laboratory findings of DIC
- thrombocytopenia
- prolonged PT and PTT
- low fibrinogen (b/c its all being used up)
- increased levels of D-dimer (fibrinogen degredation products)
- Schistocytes (helmet cell)
- low levels of ATIII, Protein C and S, factors V, VIII, X, XIII
49
Treatment of DIC
tx is targeted at underlying cause.
ex. sepsis- treat the infection
- anticoagulants only to prevent imminent death
- platelets or coagulation factor replacement in the case of platelets 100mg/dL if significantly elevated PT/INR
50
What things stimulate clottting?
- endothelial damage and inflammation
- -atherosclerosis
- -DM
- -Tobacco use
- -cancers
-elevated platelet levels
51
Conditions and risk factors that accelerate the activity of the clotting system?
- Pregnancy
- oral contraceptives
- postsurgical state
- malignancy
- hereditary clotting disorders
Risk factors:
-stasis/immobility
- low cardiac output (CHF)
- obesity (extra body fat has increased estrogen levels, estrogen levels increase coagulation)
- sleep apnea
52
What are the hereditary clotting disorders?
- Protein C
- Protein S
- Antithrombin III
- Factor V leiden
- Anti-phospholipid aby
53
How does protein C deficiency affect hemostasis?
-Protein C inactivates Factor V and VIII thereby inhibiting coagulation, in the event of DEFICIENCY, the actions of factor V and VIII lead to excessive clotting
54
Signs and symptoms of Protein C deficiency
- usually no signs or sx are recongnized until clots form.
- -thrombosis
- -deep vein thrombosis
- -PE
- -Thrombophlebitis
55
What tests do you order when working up Protein C deficiency?
- Protein C
- PTT, PT
- Thrombin time
- Bleeding TIme
- Medical and family hx may be revealing of hx of thromboebolism
56
-Tx of Protein C deficiency
- treat w/ anticoagulants if high risk for clotting (surgery/hospitalization)
- Chronic anticoagulation if hx of thrombosis (only do this if they have hx of clots)
57
Protein S function?
-supports the function of protein C, its needed fro proper function of Protein C.
58
How does Protein S deficiency affect hemostasis?
-a deficiency in protein S results in diminished ability of protein C to inactivate factors V and VIII resulting in excessive clotting.
59
Symptoms, Dx, and tx of Protein S deficiency
-these are all the same as protein C deficiency.
Sx:
- usually no signs or sx are recognized until clots form.
- -thrombosis
- -deep vein thrombosis
- -PE
- -Thrombophlebitis
Tx:
-treat w/ anticoagulants if high risk for clotting (surgery/hospitalization)
-Chronic anticoagulation if hx of thrombosis (only do this if they have hx of clots)
60
How do you get antithrombin III deficiency? At what ages is this disorder most common?
- hereditary disorder, autosomal dominant
| - 15-35years
61
What are the symptoms of Anti-thrombin III deficiency?
- recurrent venous thrombosis*
- Pulmonary embolism
- repetitive intrauterine fetal death
62
Function of ATIII?
inhibitor of thrombin, factors X and IX
63
How does ATIII deficiency affect hemostasis?
-leads to tendency to form clots
64
Work up if suspected ATIII deficiency? Tx?
- Antithrombin-heparin cofactor assay (measures functional AT activity) is the best screening test for AT deficiency
- if pt on anticoagulatn or in midst of thrombotic crisis the test results can be skewed.
- PT and PTT should be normal.
- Same as Protein C and S deficiency
65
What is the most common genetic disorder to cause DVT?
Factor V Leiden, normal amount of factor V but its mutated so it doesnt function normally
66
How does Factor V Leiden deficiency affect hemostasis?
- blood has increased tendency to clot and is most likely to occur in the veins.
- Lack of Factor V Leiden decreases the anticoagulant activity of the activated protein C.
67
Sx of Factor V Leiden deficiency?
- asymptomatic until clot forms resulting in ....
- Thrombophlebitis
- deep vein thrombosis
- Pulmonary embolism
68
Factor V Leiden deficiency Tx
- chronic coagulation if presenting w/ blood clots
| - if no hx of thrombosis then only use anticoagulants if at risk for clots d/t hospitalization or surgery
69
what is Antiphopholipid Aby syndrome?
| How does this affect hemostasis?
- clotting disorder secondary to autoimmune process.
- autoimmune hypercoaguable state caused by antiphospholipid abys
- abys lead to arterial and venous clot formation
70
Complications of Antiphopholipid Aby syndrome?
-pregnancy: miscarriage, stillbirth, preterm delivery, severe eclampsia
end organ damage
71
What are the types of Antiphopholipid Aby?
- Lupus anti-coagulant
- Anti-cardiolipin aby
- Anti-beta2-glycoprotein
72
What are the primary and secondary causes of Antiphopholipid Aby syndrome?
Primary: no other related disease to cause abnormal abys
-other autoimmune disorders such as lupus
73
Dx of Antiphopholipid Aby Syndrome
Must have one of the abnormal bays PLUS hx of clotting
- anti-cardiolipi abys IgG or IgM
- lupus anticoagulant
- anti-beta2glycoprotein I IgG and/or IgM
74
Tx of Antiphopholipid Aby Syndrome
-chronic anticoagulation and antiplatelet therapy:
Aspirin
Warfarin
