Bleeding Disorders 2 Flashcards
how does hypersplenism affect platelet mass? what about a splenectomy?
hypersplenism —> platelet sequestration, more platelets reside here (~30 —> 70%)
in splenectomy, platelet count may rise because there is more in circulation
schistocytes suggest….
schistocytes = RBC fragments (alarming finding!)
indicate mechanical injury to RBC, such as by microthrombi formation —> microangiopathic intravascular hemolytic anemia
will present with low platelet count
hemolytic anemia + low platelet count + schistocytes =
microangiopathic hemolytic anemia: intravascular hemolysis of RBC due to sheering by microthrombi
(microthrombi cause platelets to be consumed)
3 important causes of microangiopathic hemolytic anemia are:
- hemolytic uremic syndrome
- thrombotic thrombocytopenia purpura
- disseminated intravascular coagulation (DIC)
describe what causes hemolytic uremic syndrome and how it presents
what kind of disorder is this?
hemolytic uremic syndrome: type of microangiopathic hemolytic anemia (intravascular)
triggered by E. coli diarrheal illness (acquired or hereditary), damage via Shiga toxin
—> thrombocytopenia, bloody diarrhea, acute kidney injury (damage to glomerular capillaries), schistocytes and helmet cells
Pt is a 4yo F brought to ED for bloody diarrhea and fever. Stool sample comes back + for E. coli, and lab results indicate thrombocytopenia and Hgb <8g/dL, and elevated BUN and creatinine.
What type of anemia is the pt suffering from? What would you see on a peripheral smear?
Hemolytic Uremic Syndrome, type of microangiopathic hemolytic anemia (intravascular) - acquired or inherited
Shiga toxin of E. coli damages capillary endothelium, microthrombi causes RBC fragmentation
peripheral smear will show schistocytes and helmet cells
elevated BUN (blood urea nitrogen) and creatinine indicate kidney damage (toxin damages glomerular capillaries)
what is the classic presentation of thrombotic thrombocytopenic purpura (3)? what kind of illness is this?
thrombotic thrombocytopenic purpura: microangiopathic hemolytic anemia (microthrombi damage RBC)
- malaise + fever + fatigue
- acute onset of hemolytic anemia + thrombocytopenia
- mild to severe CNS dysfunction - stroke, seizure, coma when severe
what is the cause of thrombotic thrombocytopenic purpura, a type of microangiopathic hemolytic anemia?
severe deficiency in ADAMTS13 (usually due to acquired autoantibody) - needed to cleave Von Willebrand Factor multimers into smaller pieces that circulate (which chaperone Factor VIII, facilitate platelet adherence)
long multimers cause platelets to attach, microthrombi to form (like a big net for platelets)
A 36yo F presents with fever, severe headache and confusion, and multiple bruises on both legs. On PE, pt was noted to have a slight murmur. Lab results indicate low Hgb, low platelet count, high LDH, but negative Direct Coombs test. Peripheral smear shows schistocytes. Pt has a normal clotting profile. Pt. is negative for infection or pregnancy.
What is going on? What should you do for this patient?
thrombotic thrombocytopenic purpura: type of microangiopathic hemolytic anemia due to autoantibodies against ADAMTS13 (cleaves VWF)
large VWF multimers act like net to platelets
present with CNS dysfunction (mild to severe), signs of intravascular hemolytic anemia (v height LDH), thrombocytopenia, schistocytes
start plasma exchange - TPP can be life-threatening, begin treatment based on suspicion without definitive diagnosis
what is disseminated intravascular coagulation (DIC) initiated by? what does this cause?
external trigger (septic shock, traumatic injury, pregnancy)
release of/exposure to tissue factor, exposure of blood to pro-coagulants —> systemic activation of clotting cascade
consumptive coagulopathy: widespread microthrombi deplete clotting factors and platelets, so clotting and bleeding from different locations happening at once —> end organ damage
[type of microangiopathic hemolytic anemia]
how is DIC diagnosed?
- abnormal clotting profile: clotting factors are all consumed
- fibrinolysis: anti-coagulation factors also consumed, elevated D-dimers (fibrin degradation product)
- schisctocytes (sign of microangiopathic hemolytic anemia)
- signs of intravascular hemolysis (high LDH)
One of the patients on your floor is found in the morning with many bruises that formed overnight. Both coagulative and anti-coagulative proteins/factors are low, PTT is high, D-dimers are high, and schistocytes are noted in peripheral smear. What is going on?
DIC: disseminated intravascular coagulation, type of microangiopathic hemolytic anemia, life-threatening
triggered by external event, such as trauma or sepsis —> systemic activation of coagulation cascade, which consumes both pro- and anti- coagulation proteins
if a patient is showing signs of bleeding, but platelet count and PT/aPTT are normal, there is a:
a. problem with platelet number
b. problem with platelet function
explain how your answer can be further assessed
problem with platelet function
assess with:
- bleeding time: assess primary hemostasis (platelet function), not used anymore
- platelet aggregometer: patient’s plasma + platelets + agonist, measure how long it takes platelets to aggregate
how are platelet agonists and Ristocetin used, respectively, to test platelet function?
platelet aggregometry: patient’s plasma + platelets + agonists
agonists (ADP, epinephrine, collagen): activate GpIIb/IIIa (platelet receptor) —> induce aggregation
Ristocetin: enchances interaction of VWF with platelet receptor GbIb/IX/V —> platelet agglutination (clumping)
Most common inherited bleeding disorder (AD inheritance) that can be due to a qualitative or quantitative deficiency of ____. Can affect both primary and secondary hemostasis. What is?
Von Willebrand Disease: deficiency (# or function) of VWF, usually affects primary hemostasis (secondary if severe because of decreased Factor VIII)
—> skin bleeding (bruising), bleeding from mucosal surfaces (nose bleeds, heavy meses, GI bleeding if severe)
fail to respond to ristocetin, which enhances VWF binding to platelet receptor GbIb
You’re on pediatric rounds taking a history of a 13yo F. She says she has heavy menses and bruises easily, like her mom. She also notes getting nosebleeds that las more than 10 minutes. CBC, platelet count, and coagulation studies come back normal. However, there is no response to ristocetin. What differential diagnosis does this require you to make, and what is likely going on?
Von Willebrand Disease: AD deficiency in VWF (essential for platelet adhesion), most common inherited bleeding disorder
failure to respond to ristocetin (enhances VWF interaction with platelet receptor GPIb) can be due to deficiency in VWF or platelet receptor - should follow with a ristocetin co-factor assay (using control platelets)
this AR bleeding disorder is caused by GpIIb/IIIa receptor deficiency, and may present as early as infancy or in adulthood.
what is?
Glanzmann thrombasthenia
what is Glanzmann thrombasthenia and how does it present?
AR inherited deficiency in platelet receptor GpIIb/IIIa (for fibrinogen)
—> prolonged bleeding time, platelets fail to aggregate with agonist stimulation (but ristocetin response intact)
—> mucocutaneous bleeding (nose, bruise, gum, GI, menorraghia)
how would you diagnose Glanzmann thrombasthenia? how would you treat it?
Glanzmann thrombasthenia: AR definitely in platelet receptor GpIIb/IIIa (for fibrinogen)
- prolonged bleeding time
- fail to aggregate with agonist, but ristocetin response intact
- flow cytometry shows lack of GpIIIa
—> platelet transfusion
Your patients is an 11yo M coming to you with recurrent epistaxis (nose bleed) and GI bleeding. Their parent says they tend to bruise easily so avoid playing sports, similar to their maternal grandfather. Their platelets fail to aggregate with a typical agonist, but the ristocetin response is intact. What is likely going on? What test will you use to confirm your presumptive diagnosis?
Glanzmann thrombasthenia: AR deficiency in platelet receptor GpIIb/IIIa (for fibrinogen)
can present infancy through adulthood depending on severity
confirm with flow cytometry
This AR bleeding disorder is due to a deficiency in GpIb/IX/V receptor for VWF. What is?
Bernard-Soulier Syndrome: AR deficiency in GpIb/IX/V receptor (For VWF) —> defective platelet adhesion or development
low platelet count and giant platelets on peripheral smear
describe the cause and effect of Bernard-Soulier Syndrome, including how it presents
Bernard-Soulier Syndrome: AR bleeding disorder due to deficiency of GpIb/IX/V platelet receptor for VWF —> defective platelet adhesion and development
—> mild mucocutaneous bleeding (nose most common, bruising, GI bleeding, menorraghia)
low platelets and giant platelets
how do you diagnose and treat Bernard-Soulier Syndrome?
Bernard-Soulier Syndrome: AR bleeding disorder due to deficiency of GpIb/IX/V platelet receptor for VWF
—> history of mild mucocutaneous bleeding (esp. nose), low platelet count, giant platelets, prolonged bleeding time, fail to aggregate with ristocetin + VWF
—> supportive treatment, avoid anti-platelet drugs
Pt is 17yo F coming to you about her menorraghia. While taking her history, you note epistaxis (nose bleed) and bruising that seems more often than normal. FHx includes a grandmother who had frequent bruising. You take a peripheral smear and note giant platelets.
What is likely causing her bleeding?
Bernard-Soulier Syndrome: AR bleeding disorder due to deficiency of GpIb/IX/V platelet receptor for VWF
giant platelets, fail to aggregate with ristocetin
how does uremia affect platelet function
uremia: loss of kidney function, associated with end-stage renal disease
toxins released, which cause platelet dysfunction
*acquired platelet dysfunction
platelet deficiencies will show bleeding _____,
whereas coagulation deficiencies will show bleeding ______
platelet issues —> skin bleeding (bruising)
coagulation issues —> deep tissue bleeding, hemarthrosis (bleeding into joints), hematoma (collection of blood)
what deficiency causes hemophilia A, B, and C, respectively?
hemophilia A: Factor VIII (8)
hemophilia B: Factor IX (9)
hemophilia C: Factor XI (11)
How can you diagnose Hemophilia A?
Hemophilia A: factor VIII (8) deficiency
- aPTT is prolonged - intrinsic pathway test (Factor 12, 11, 9, 8)
- mixing study: determine factor deficiency vs presence of inhibitor - mix with control plasma, correction = factor deficiency (if results not corrected, there is an inhibitor present, such as alloantibodies)
- low von willebrand factor activity (chaperone for Factor VIII)
T/F: Hemophilia A and B are clinically indistinguishable
TRUE: same things happen
hemophilia A: Factor VIII (8)
hemophilia B: Factor IX (9)
