Platelet Disorders Flashcards
What are the signs and symptoms of platelet bleeding (i.e., primary hemostasis)?
- mucouos membrane bleeding
- epistaxis
- prolonged oozing from minor wounds
- brusing
- menorrhagia
- abnormal intraoperative bleeding
What is thrombocytopenia?
low platelet counts
What is a failure of secondary hemostasis?
- bleeding from large vessels
- subcutaneous hematomas
- hemarthroses
- intramuscular hematomas
This is a more “coagulation factor deficiency” picture
What are some signs of congenital thrombocytopenia?
- umbilical cord stump bleeding
- bleeding after circumcision that won’t stop
When you see bruising on a person with suspected thrombocytopenia, what distinguishes it from ordinary bruising?
- indurated (hardened)
- found in locations where simple trauma bruises are unlikely (e.g, abdomen)
- sometimes accompanied by petechiae
What are the etiologies of thrombocytopenia?
Poor platelet production
- bone marrow failure
- infections
- drugs (sulfa)
- nutritional disorders (B12, folate)
- inherited
Increased destruction of platelets
- splenomegaly
- non-immune mediated (DIC, HUS)
- immune-mediated platelet destruction
What do normal platelets look like?
- purple color
- small (much smaller than RBC)
- little fuzzy granulations
- count and multiply in a field by 10k to get total
What is immune thrombocytopenia (ITP)?
immune system mediated destruction of platelets.
What do the practice guidelines from ASH 2011 say about treatment of ITP?
- mild symptoms (i.e., no “wet” bleeding) can be treated with observation alone
- First line treatment includes corticosteriods, IVIG or anti-D immunoglobin
- Adults: consider for platelet less than 30x109/L try corticosteriods first, IVIG if rapid or IVIG/Anti-D if you can’t do steroids
- Kids: probaby will use IVIG/Anti-D FIRST as corticosteroids can MASK underlying Leukemia and hide the diagnsosis from you.
What are the pratical considerations in treating ITP?
- no bright line rules for platelet levels
- Individualize decisions based upon:
- patient age (little people are dangerous)
- clincal symptoms
- platelets
- parent/your concern
- access to medical care (ER)
- Patients at high risk of significant bleeding should be treated and monitored
What are the symptoms of TTP?
- Note: Rare (congenital < acquired)
- “Classic” Pentad: thrombocytopenia; microangiopathic hemolytic anema; fluctuating neurological signs; renal impairment; fever.
- Most patients present WITHOUT the full pentad
How do you diagnose TTP?
- ADAMTS13 below normal range is definitive
- Normal (<5-10%)
- Positive ADAMTS13 inhibitor = usually acquired
- Negative ADAMTS13 inhibitor = indicates congenital TTP (Upshaw-Schulman Syndrome)
What does ADAMTS-13 Do?
- It is an enzyme that cleaves von Willebrand multimers
- It is essential to prevent excessive clot formation
- low ADAMTS-13 causes multimers to form webs in vessels
- RBC’s get sheared causing shistocytes
- platelets get caught in the webs, reducing their numbers
What is Hemolytic Uremic Syndrome (HUS)?
A disease that causes microangiopathic hemolytic anemia; thrombocytopenia; and renal impairment (predominant)
- What is the most common cuase of HUS?
- shiga-toxin producing E. Coli (STEC)
absence of this classified as atypical (aHUS)
- leads to uncontrolled activation of the complement system
What genetic mutation is commonly seen in patients that acquire aHUS?
- 60% have mutation in genes that protect us from complement activation (Factor H - CFH) and I (CFI)
Who is most likely to get HUS?
- Manifests in all ages (note that this is NOT what PPP says)
- especially in adolescents and adults
What is the threatment for HUS?
- Primarily supportive
- transfusions may be required for anemia
- platelet transfusion only resereved for severe bleeding
- dialysis as need for renal
- watch fluid load
What is the prognosis for people with HUS?
- Generally favorable - renal recovery
- hematologic manifestations typically resolve 1-2 weeks
What is the treatment for aHUS?
- Plasma exchange
- Eculizamab - MAb to complement factor C5
- blocks complement activation
What is the prognosis for aHUS?
Compared with HUS, prognosis is much poorer. Chronic relapsing course is common and outcome overall is poorer.
What is the etiology of immune thrombocytopenia?
- may present 1-2 weeks after an immune trigger
- viral illness
- live virus immunization
- allergic rxn
- can be presenting symptom of broader immune disease (HIV, SLE)
- can be brought on by specific infections - HepC and H. Pylori
- lymphoid malignancy
What is the pathophysiology of congenital TTP?
- Gene that makes ADAMST13 is mutated, resulting in lowered production of the enzyme
What is the pathophysiology of immune-mediated TTP?
- B-cell mediated autoantibody production against von Willebrand cleaving protease (ADAMS13)
How do you treat TTP?
- early diagnosis crucial - DO NOT MISS
- plasmapheresis is the main treatment
- replaces ADAMST13 and reduces any antibody
- in acute phase, 1.5 L
- maintains congenital 3-4 weeks
- steroids for immune-mediated TTP
- Platelet transfusions contraindicated unelss bleeding is life-threatening
What is the second-line treatment for TTP if plasmaphoresis fails?
- Immune mediated:
- splenectomy
- corticosteriods
- rituximab (MAb - 95% of case reports)
What is secondary hemostasis (coagulative factor bleeding)?
- bleeding from large vessels
- subcutaneous hematomoas
- hemarthroses - bleeding into joint spaces
- intramuscular hematomas
What is pseudothrombocytopenia?
Where platelet counts are artificially reduced on CBC/peripheral smears because the platelets have all aggregated into clumps (improper handling of sample).
What is the epidemiology of ITP?
- all genders, races and ages (used to be thought of as a young woman’s disease - not true)
- 10-40 per 100k prevalence
What are the categories of ITP?
- Acute: within three months of diagnosis
- persistent: 3-12 months from diagnosis (80% of ITP in childhood will spontaneously resolve in 6-12 months)
- chronic ITP: lasting more than 12 months (80% of adult cases go on to be chronic)
What is the pathophysiology of ITP?
- loss of self-tolerance
- autoantibodies (IgG) against platelet antigens
- platelet gycoproteins (IIb/IIIa and Ib/IX)
- cellular mechanisms
- platelets get coated with autoantibodies
- get destroyed (retiuloendothelial system) - bind to Fc receptros on macrophages, then get eaten
- decreased production
What is the key point to know about the pathophysiology of ITP?
Polyclonal autoantibodies may inhibit platelet production by inhibiting megakaryocyte maturation
What is the clinical presentation of ITP?
- bleeding
- mucocutaneous bleeding
- wet -oral bullae, epistaxis, menorrhagia, gingival and GI bleeding
- dry - bruising and petechiae
- mucocutaneous bleeding
What does the CBC/PBS of ITP look like?
- thrombocytopenia <100 x 109/L
- normal platelet granulation
- occasional large platelets
- normal WBC # and diff
- normal RBC # and appearance (unless active bleeding)
- no evidence of hemolysis
How do you diagnose ITP?
- Diagnosis of exclusion
- no splenomegaly, lymphadenopathy
- other CBC indices normal
ITP in adults - what additional tests should be done for new onset?
- Test for HIV and HCV
- broader immune dysfunction
- DAT - prior to anti-D
- quantiative immunoglobins
What are the treatments for ITP?
- IVIg
- anti-D
- corticosteroids
What is IVIG treatment?
- derived from human plasma
- blocks Fc receptors on macrophages from binding with autoantibody coated platelets
- adverse effects include nausea, vomiting, headache (also sx of head bleed), fever
- aceptic meningitis (rare)
- alloimmune hemolysis (rare)
- infection transmission exceedingly rare
- anaphylaxis in IgA deficient pt.
What are the pros and cons of IVIG?
Pros
- lack of long term side effects
- efficacious in 1-2 doses (lasts 2-4 wks)
Cons
- several hour IV infusion
- very $$$
- difficult side effects
- derived from pooled human plasma
What is Anti-D immunoglobin therapy?
- polyclonal Ab derived from human Ig
- Rh(D) antigen positive, non-splenectomized pts can receive
- preferential destruction of antibody-coated RBCs, spares the platelets (sacrifices RBC)
- adverse events: fever, chills, nausea, vomiting (give premedications)
What are the pros and cons of Anti-D therapy?
Pros
- short IV infusion
- efficacious
- fewer donors per dose than IVIG
Cons
- side effect of hemolysis
- really small chance <0.05% massive intravascular hemolysis
- no no if baseline hemolysis (DAT/Coombs BEFORE starting therapy)
- have to avoid in anemia, acute illness, abormal renal function, patients > 65
What is the biggest risk to avoid in ITP?
Intracranial hemorrhage
- rare <1%, but deadly
- patients with lowest platelet counts at highest risk <20k
- life-threatening spontaneous bleeding at very low counts
- eliminate anti-platelet medications and high risk activity
How is corticosteriod therapy used in treating ITP?
- 1st line in adult ITP patients
- masks leukemia, so you need to avoid as first line in children
- predinose, methylprednisone, dexamethasone
- less rapid platelet rise than in other therapies
- get massive weight gain
What are the urgent treatment options for ITP?
- platelet infusions/drip
- emergency splenectomy
- IV methylprednismoe
- IVIG
- recombinant FVIIa (extrinsic pathway that will push toward clotting)
What is the treatment for chronic ITP?
- splenectomy
- effective 75%
- but many post-splenectomy complications
- Rituximab (specifically against B cells)
- thrombopoietin receptor agonists - binds to megakaryocytes and stimulates platelet production
- Azathioprine - immunosuppressant
ITP vs TTP - How do you tell them apart?
Patient Population:
Young child - suspect ITP over TTP (note congenital TTP)
Clinical Symptoms: ITP often has no symptoms other than mucocutaneous bleeding. NO splenomegaly and no hemolytic anemia or neuro symptoms.
Diagnosis: ITP is isolated thrombocytopenia, but TTP has hemolytic anemia, increased indirect bilirubin, decreased haptoglobin
