Charts Flashcards
CML
Things Must Know
- Neutrophilic leukocytosis
- Basophilia
- Philadelphia chromosome
- Three phases (chronic, accelerated, blast crisis)
Signs
Huge spleen,
Big liver,
Maybe some lymphadenopathy
Symptoms Slow onset, Fever, Fatigue, Night sweats, Abdominal fullness
Labs - ↑↑↑ WBC - Neutrophilia with left shift - Basophilia - ↓ hemoglobin - ↑ platelet count (at first) - ↓ LAP (leukocyte alkaline phosphatase) - Cytogenetics: t(9,22) → BCR-ABL (tyrosine K & IgL)
Treatment
- Imatinib (Gleevac)
Remission:
- Hematologic: WBC <10K, normal morphology, Hgb, Plt
- Cytogenetic: no M phase, t(9;22)
- Molecular: no BCR-ABL
Leukemic transformation can occur
Polycythemia
Vera (PV), aka primary
Things Must Know
- High RBC (makes blood sludgy)
- Different from secondary polycythemia
- Thrombosis and hemorrhage
- Jak-2 mutation
Signs
- Headache
- Pruritis
- Dizziness
- Thrombosis (due to sludgy-ness of blood)
- Infarction
Symptoms
Big spleen, liver
Plethora (red face)
Labs ↑ red cell mass Normal O2 saturation Thrombocytosis ↑ WBC without infection ↑ LAP – not sure why… ↑ B12 – abnormal B12 metabolism
Treatment
- Phlebotomy
- Maybe myelosuppressive drugs
- Roluxinib (sp?)
Median survival: 9-14 years
Death from thrombosis or hemorrhage; can undergo leukemic transformation in some
Essential Thrombo-cythemia
Things Must Know
- Very high platelet count in blood
- Can occur in young women (~30s)
- Diagnosis of exclusion
- Thrombosis and hemorrhage
Signs
Purpura, bruising, Pallor, tachycardia, Biggish spleen
Symptoms
Bleeding, Thrombosis
Labs
- Platelet count >600,000
- Hgb <13 or RBC mass normal
- No Philadelphia chromosome
- No marrow fibrosis
- No other reason for thrombocytosis
Treatment
- Platelet pheresis
- Maybe myelosuppressive drugs
- Aspirin
Median survival: 5-8 years
Death from thrombosis or hemorrhage; can transform into acute leukemia
Chronic Myelofibrosis
Things Must Know
- Panmyelosis…
- …then marrow fibrosis
- Extramedullary hematopoiesis
- Teardrop red cells
Signs
Huge spleen, Pallor, tachycardia
Symptoms
Left upper quadrant fullness, Weakness, fatigue, palpitations
Labs
Treatment
Left upper quadrant fullness, Weakness, fatigue, palpitations
CLL/SLL
Things Must Know
- Small, mature lymphocytes
- = small lymphocytic lymphoma (SLL)
- B-cell, but CD5+ (Pan-T cell marker; weird!)
- Long but inexorable course
Clinical Findings
- Older (>40)
- Asymptomatic at first
- Later, organ infiltration
- Infection may occur due to hypogammaglobulinemia
Immunophenotype
- Positive for: B-cell antigens (CD20), A T-cell antigen (CD5)!
- Negative for: TdT
Treatment
- Conservative (tx can be worse than leaving it alone)
- Reduce organomegaly, infections
Mean survival: 9 yrs
Death from infection
Hairy Cell Leukemia
Things Must Know
- Hairy cells
- Splenomegaly without lymphadenopathy
- Pancytopenia
- TRAP +
- B cell neoplasm
Clinical Findings
- Older (>40)
- M:F = 5:1
- Big spleen but no lymphadenopathy!
- Pancytopenia (usually) and monocytopenia (always)
Immunophenotype
Cytochemistry: TRAP+ (red)
- Positive for B-cell antigens
- Negative for CD5
Treatment
Chemotherapy (Rituximab, IFNα?)
Good! Usually 10+ years
Prolymphocytic Leukemia
Things Must Know
- Prolymphocytes
- Splenomegaly without lymphadenopathy
- Rare
- Aggressive (< survival)
Clinical Findings
- Splenomegaly without lymphadenopathy
- Aggressive
Immunophenotype
- ↑↑ WBC (~50K)
- ↓ Hgb
- ↓ platelet count
Treatment
Condensed chromatin with nucleoli (weird!)
Large Granulated Lymphocyte Leukemia
Things Must Know
- Large granulated lymphocytes
- T-cell (+ granules)
- Neutropenia → recurrent infections
- Long survival
Clinical Findings
Infections (from neutropenia)
Immunophenotype
Modest leukocytosis
Neutropenic
Treatment
Long survival
Hereditary Bleeding Disorder:
von Willebrand Disease (vWD)
Things Must Know
- Most common hereditary bleeding disorder
- Autosomal dominant
- vW factor decreased (or abnormal); carries VIII (intrinsic pathway)
- Variable severity
- Three types (1, 2, 3)
Symptoms
- Mucosal bleeding in most patients
- Deep joint bleeding in severe cases
Lab Tests
- Bleeding time: prolonged
- PTT: prolonged (“corrects” with mixing study)
- INR: normal
- vWF level decreased (normal in type 2)
- Platelet aggregation studies abnormal
- Ristocetin assay
Treatment
- DDAVP (raises VIII and vWF levels)
- Cryoprecipitate (contains vWF and VIII)
- Factor VIII (don’t give all the time, since body will make Ab against it)
Hereditary Bleeding Disorder:
Hemophilia A
Things Must Know - Most common factor deficiency - X-linked recessive in most cases *(30% are random mutations) - Factor VIII level decreased (intrinsic pathway) Variable amount of “factor” bleeding
Symptoms
- Severity depends on amount of VIII
- Typical “factor” bleeding
- deep joint bleeding
- prolonged bleeding after dental work
- Rarely, mucosal hemorrhage
Lab Tests
- INR, TT, platelet count, bleeding time: normal
- PTT: prolonged (“corrects” with mixing study)
- Factor VIII assays: abnormal
- DNA studies: abnormal
Treatment
- DDAVP
- Factor VIII
Hereditary Bleeding Disorder:
Hemophilia B
Things Must Know
- Factor IX level decreased (intrinsic pathway)
- Much less common than hemophilia A
- X-linked recessive in most
- Same clinical and laboratory findings
Symptoms
- Severity depends on amount of VIII
- Typical “factor” bleeding
- deep joint bleeding
- prolonged bleeding after dental work
- Rarely, mucosal hemorrhage
Lab Tests
- INR, TT, platelet count, bleeding time: normal
- PTT: prolonged (“corrects” with mixing study)
- Factor VIII assays: abnormal
- DNA studies: abnormal
Treatment
- DDAVP
- Factor VIII
Hereditary Platelet Disorder:
Bernard-Soulier Syndrome
Things Must Know
- Abnormal Ib
- Abnormal adhesion
- Big platelets
- Severe bleeding
Treatment
Platelets as big as RBCs!
Hereditary Platelet Disorder:
Glanzmann Thrombasthenia
Things Must Know
- No IIb-IIIa
- No aggregation
- Severe bleeding
Hereditary Platelet Disorder:
Gray Platelet Syndrome
Things Must Know
- No α granules (vWF, fibrinogen, etc.)
- Big, empty platelets
- Mild bleeding
Hereditary Platelet Disorder:
Granule Deficiency
Things Must Know
- No δ granules (Ca2+, ADP, ATP, 5HT)
- Can be part of syndrome (e.g., Chediak-Higashi)
Acquired Bleeding Disorders:
DIC
Most Common Causes
- Malignancy (APL)
- OB complications
- Sepsis
- Trauma
Things Must Know
- Lots of underlying disorders
- Something triggers coagulation, causing thrombosis
- Platelets and factors get used up, causing bleeding
- Microangiopathic hemolytic anemia (MAHA)
Symptoms
- Insidious or fulminant
- Multi-system disease
- Thrombosis and/or bleeding
Lab Tests
- INR, PTT, TT prolonged
- FDPs: increased
- Fibrinogen: decreased
Treatment
- Treat underlying disorder
- Support with blood products
Acquired Bleeding Disorders:
ITP (Idiopathic Thrombocytopenia Purpura)
Things Must Know
- Antiplatelet antibodies
- Acute vs. chronic
- Diagnosis of exclusion
- Steroids or splenectomy
Pathogenesis:
- Autoantibodies to GpIIb-GpIIIa or Ib
- Binds to platelets
- Splenic macrophages eat platelets
Symptoms
- Chronic
- Adult women
- Primary or secondary
- Insidious: easy bruising, nosebleeds
- Danger: bleeding into brain
- Acute
- Children
- Abrupt; follows viral illness
- Usually self-limiting
- May become chronic
Lab Tests
- Signs of platelet destruction:
- thrombocytopenia
- normal/increased megakaryocytes
- big platelets
- INR/PTT normal
- No specific diagnostic test for ITP
Treatment
- Glucocorticoids
- Splenectomy
- Intravenous immunoglobulin (IVIG)
Acquired Bleeding Disorders:
TTP
Thrombotic Thrombocytopenic
Purpura
Things Must Know
- Pentad: MAHA, thrombocytopenia, fever, neurologic defects, renal failure
- Deficiency of ADAMTS13
- Big vWF multimers trap platelets
- Plasmapheresis or plasma infusions
Symptoms
- Hematuria, jaundice (MAHA)
- Bleeding, bruising (thrombocytopenia)
- Fever
- Bizarre behavior (neurologic deficits)
- Decreased urine output (renal failure
Lab Tests
Pathogenesis of TTP:
- Just-released vWF is unusually large (UL)
- UL vWF casues platelet aggregation
- ADAMTS13 cleaves UL vWF into less active bits
- TTP is due to ADAMTS13 deficiency
Treatment
- Acquired TTP: plasmapheresis
- Hereditary TTP: plasma infusions
Acquired Bleeding Disorders:
HUS
Hemolytic Uremic Syndrome
Things Must Know
- MAHA and thrombocytopenia
- Epidemic (E. coli) vs. non-epidemic
- Toxin (or ?) damages endothelium
- Treat supportively
Symptoms Epidemic: - Children, elderly - Bloody diarrhea, then renal failure - Fatal in 5% of cases Non-epidemic: - Renal failure - Relapsing-remitting course - Fatal in 50% of cases
Lab Tests Pathogenesis Epidemic: - E.coli O157:H7 (raw hamburger) - Makes nasty toxin - Injures endothelial cells Non-epidemic: - Defect in complement factor H - Inherited or acquired
Treatment
- Supportive care
- Dialysis
- NOT antibiotics (may increase toxin release!)
AML-M0
Old Classification System
Important Characteristics
- ↑↑↑ myeloblasts (»20% → ~90%)
- Bland – minimal differentiation
- MPO (myeloperoxidase stain) negative
- Need markers → flow cytometry
