coagulation disorders Flashcards
i. Platelets are actively inhibited by
the endothelial lining of blood vessels (via NO and ADPase)
Endothelial injury exposes collagen and releases ________, which activates platelets
Endothelial injury exposes collagen and releases von Willebrand’s Factor (vWF), which activates platelets
using GP Ia, actin, and myosin platlets _____ toexposed collagen
platlets adhere to exposed collagen with myosin GP Ia, actin,
Platelets aggregate, using
vWF and fibrinogen
a blood clot is composed of
Fibrin
platlets
erythrocytes
these proteins work to inactivate clotting factors
b. Protein C (activated by Protein S) and antithrombin work to inactivate clotting factors
TFPI inhibits
tissue factor pathway inhibitor
inhibits Xa and thrombin
this is the enzyme that converts plasminogen to plasmin
tPA
tisse plaminogen activator
bleeding disorders can be
due to a platelet issue
due to a clotting issue
congenital or aquired
these types of bleeding disorders usually effect the skin and muscles
clotting
this type of bleeding disorder usually involves the skin and mucosa
platelet disorders
congenital bleeding disorders usually effect
vascular integrity platelet function fibrinolysis or coagulation factors
types of acquired bleeding disorders
involves multiple systems: liver, kidney, collagen, immune)
i. Cancer, infection, shock, obstetrics, malabsorption, AI disorders
ii. Drugs (NSAIDs, aspirin, thiazides, anticoagulants)
laboratory studies that can be done to assess bleeding disorders
Platelet count, peripheral smear, bleeding time
Prothrombin time (PT), partial
thromboblastin time (PTT), activated
PTT, or INR
1.0 is normal INR
The higher the PT time, the less likely we are to clot normally
Thrombin clotting time (measures rate of conversion between fibrinogen and fibrin)
iv. Some problems may require more specialized studies
The most common cause of abnormal bleeding
and what is it
Thrombocytopenia
Abnormal decrease in the number of platelets
what causes thrombocytopenia
impaired production, increased destruction, splenic sequestration, dilution
usual presentation of thrombocytopenia
d.Usual presentation is petechiae and/or purpura on the skin and mucous membranes
ITP: Idiopathic Thrombocytopenic Purpura
what populations do we see with this acutely
Acute: most commonly in children, self-limited, autoimmune, associated with a recent viral URI
Abrupt appearance of petechiae, purpua, or even hemorrhagic bullae on skin and mucous membranes
ITP: Idiopathic Thrombocytopenic Purpura
what type of chronic dz do we see
Chronic: any age (20-50 most commonly), more common in women, often associated with other autoimmune disorders
Usually milder (petechiae only)
lab findings ITP
" Decreased platelets o Acute: 10,000 - 20,000/uL o Chronic: 25,000 - 75,000/uL " Possible mild anemia " Peripheral smear shows megathrombocytes " Coags (PT, PTT, INR) are normal
Treatment of ITP
" Acute: usually self-limited, resolves spontaneously (May require steroids or splenectomy) " Chronic: Rarely resolves spontaneously o Initial tx: high dose prednisone o IV immunoglobulin, stem cell therapy o Splenectomy
disorders of platelet function are most commonly
May be congenital (many possible causes) or acquired (drugs - ASA or other NSAIDs, clopidogrel/Plavix - uremia, alcoholism, hypothermia, malnutrition)
More commonly it is acquired
this is not an issue of too few like in ITP but rather funky guys
rare but often fatal. Occurs in previously healthy patients, between 20-50, more often in women, sometimes in people w/ HIV
a. Thrombotic thrombocytopenic purpura (TTP
is like TTP but found in children
i. Can be fatal
b. Hemolytic-uremic syndrome (HUS)
causes generalized bleeding in people w/ severe underlying illness (e.g., sepsis, cancer)
i. When people go into shock or septic, their entire clotting system can collapse
disseminating intravascular coagualtion
pathophys of disseminating intravascular coagulation
what is the treatment
Caused by abnormal aggregation of platelets, which both impairs their ability to function normally, AND can cause microvascular infarcts (losing fingers, losing end of their nose, losing their penis)
Transfusion, steroids, plasmapheresis(filters out their blood - abnormal platelets, etc)
Autosomal dominant, congenital bleeding disorder
and the most common type
c. Von Willebrand’s Disease
iii. There are six different types. Type I accounts for 80% of all cases. Most cases are mild
Factor VIII is bound to vWF while inactive in circulation
Factor VIII degrades rapidly when not bound to vWF
what does vWF do
Binds to collagen, binds to platelets, and binds to Factor VIII
factor VIII is released from vWF by
v. Factor VIII is released from vWF by the action of thrombin
what is the defect seen with vWF
The defect in von Willebrand’s factor means thrombin doesn’t have enough Factor VIII to activate, so Factor X doesn’t get activated as much
Clinical features
bleeding in mucous membranes. Bleeding is exacerbated by ASA
tx of vWF
is w/ desmopressin, or transfusion of Factor VIII
In patients w/ homozygous disease, symptoms are much more severe - can be life threatening
Hemophilia A
seen only in men has to do with a defieicney in VIII
AAAAEIGHT
Hemophilia B
It’s deficiency of Factor IX
X-lined recessive, about 1 in 30,000 US male births
hallmark sign of hemophilia B
c. The hallmark sign is hemarthrosis
little boy with sad elbow
CM of hemophilia
and the Tx
XIII. Bleeding into joints (can be both A and B)
Can also have epistaxis, intracranial bleeding, hematemesis, melena, microscopic hematuria
Tends to present in childhood
Symptoms can range from very severe to mild
Treatment is Factor VIII (or IX)
b. These are the most common acquired coagulopathies
vitamin K deficiencys
how does vitamin K work
d. Vitamin K works by modifying certain proteins, preventing them from degradation
vitamin K dependent factors
coagulation cascade, including prothrombin, Protein C and Protein S, and Factors VII, IX, and X.
why would someone present with a vitamin K deficiency
May be due to poor diet, liver failure, malabsorption, malnutrition, or use of broad-spectrum antibiotics (e.g., sulfanomides)
lab findings with a acquired coagulopathy like vitamin K deficiency
” Prolonged PT
“ Sometimes prolonged PTT
“ Normal fibrinogen, thrombin time, and platelet count
tx of vitamin K deficiency
the underlying cause (which is usually obvious)
“ Parenteral Vitamin K
“ Plasma to treat acute bleeding
“ Address malnutrition & malabsorption
virchows
stasis
hypercoagulopathy
injury
CM of DVT
” Unilateral edema = most specific finding
“ Leg pain occurs in 50%
“ Homan’s sign has no + or - predictive value, and may dislodge clot
“ Leg tenderness may be present in 75% of pt’s w/ DVT “ However, it’s also found in 50% of pt’s w/o DVT
“ Pain & tenderness do not correlate w/ size, location, or extent of thrombus
“ Clinical findings of DVT (or PE) occur in just 10% of patients w/ DVT (or PE)
what helps evaluate risk for DVT
xiii. The Wells Score
1. <1 point = 3%
2. 1-2 points = 17%
3. >2 points = 75%
D-dimer assays what are they
D-dimer fibrin fragments are present in fresh fibrin clot and cross-linked fibrin, but NOT in non-cross-linked fibrin or fibrinogen
how can D-dimer assays be used
b. Elevated in trauma, cancer, sepsis, surgery
c. Therefore, the D-dimer assay can rule out a DVT, but shouldn’t be used to confirm the diagnosis
when can we rule out DVT with D-dimer
e. Negative test in a low-mod risk patient w/ a Wells score <2 rules out a DVT
when would you do a diagnostic study for DVT suspicion
- All patients w/ a positive D-dimer and all patients w/ Wells score >2 require a diagnostic study
ULS sensitivity is best for what type of DVT
a. Proximal DVT: Sensitivity 97%, NPV 99%
i. NPV = negative predictive value
b. Distal DVT: Sensitivity 73%
c. Over 90% of acute PE are from proximal, rather than distal DVT
Wells >2 and US pos
tx or nah?
treat
wells >3 uls negative ?
rule out with D dimer
wells >2 ULS Neg D dimer postitive
repeast ULS in week
wells <2 ULS positive
treat
wells>2 ULS neg
rule out DVT D dimer
goals of DVT tx
- Goals of therapy -
a. Prevent clot extension
b. Prevent acute PE
c. Prevent recurrence of DVT
what is the standard for DVT Tx
- Anti-coagulation therapy, as opposed to thrombolytic therapy, is the norm, although thrombolytics may be used in some cases
recommedned rx for DVT and limitations
a. Heparin, Warfarin (Coumadin), LMW heparin
b. Heparin and Warfarin are effective, but have 2 major limitations
i. Narrow therapeutic window
ii. Highly variable dose response among individual patients
iii. This means intensive lab monitoring
when would we use heparin
best in inpatient for rapid anticoagualtion
goal with heparin tx
i. Goal is achieving a PTT between 1.5-2.5 times upper range of normal; hospitals have predetermined protocols to achieve this
when do we use warfarin and what is the goal
ii. Warfarin is usually started with heparin therapy; goal INR is 2.0-3.0 for 2 consecutive days
advantages of LMWH
Advantages
Can be given SQ (will bypass the gut)
Longer duration, can be given once or twice daily
No monitoring necessary; response correlated w/ body weight
Lower risk of thrombocytopenia
disadvantage of LMWH
Disadvantages
“ Cost
“ Cannot be easily reversed if bleeding occurs
i. The oral anticoagulant of choice
e. Warfarin
how does warfarin work
ii. It is Vitamin K agonist. Thus, it effectively induces Vitamin K deficiency in the patient
iii. Inhibits prothrombin, Proteins C and S, and Factors VII, IX, and XI
how do we use heparin and warfarin together
Heparin is continued for 4-5 days to counteract warfarin’s initial hypercoagulability effect
Like heparin, warfarin’s effect is highly variable among individual patients
how do anticoagulants work for DVT if they are not thrombolytic
vi. B/c its effect is passive (i.e., allowing clotting factors to degrade), its effect is dependent on the half-life of clotting factors - and there are MANY factors involved
main clotting factor that we are waiting for with anticoagulant therapy
vii. The main one is prothrombin (Factor II), which has a half-life of 50 hours, and may take up to 5 days to clear completely
average daily dose of warfarin
ii. The first dose should be the clinician’s best estimate of pt’s required daily dose
Avg daily dose in a 50 yo is 6.3mg/day
Avg daily dose in a 70 yo is 3.6mg/day
Start at 5mg/day. Check INR daily, then every few days, titrate dose, until steady state
risk of fatility and bleeding with warfain
viii. 1% risk of fatality annually (closely related to age and control of INR)
ix. “Minor bleeds” are common, w/ approx. 15% annual incidence
INR <2
increase weekly dose 5-20%
INR 3-3.5
decrease weekly 5-15%
INR 3.6-4
withold 1 dose
decrease weekly 10-15%
INR>4
withold 1 dose
decrease weekly 10-20%
