Hematology and Oncology - Pathology (2) Flashcards
1
Q
Coagulation disorders
- PT
- PTT
A
- PT
- Tests function of common and extrinsic pathway (factors I, II, V, VII, and X).
- Defect –> increased PT.
- PTT
- Tests function of common and intrinsic pathway (all factors except VII and XIII).
- Defect –> increased PTT.
2
Q
Hemophilia A or B
- Type of disorder
- PT
- PTT
- Mechanism and comments
- Treatment
A
- Type of disorder
- Coagulation disorder
- PT
- No effect
- PTT
- Increased
- Mechanism and comments
- Intrinsic pathway coagulation defect.
- A: deficiency of factor VIII –> increased PTT.
- B: deficiency of factor IX –> increased PTT.
- Macrohemorrhage in hemophilia
- Hemarthroses (bleeding into joints), easy bruising, increased PTT.
- Intrinsic pathway coagulation defect.
- Treatment
- Recombinant factor VIII (in hemophilia A).
3
Q
Vitamin K deficiency
- Type of disorder
- PT
- PTT
- Mechanism and comments
A
- Type of disorder
- Coagulation disorder
- PT
- Increased
- PTT
- Increased
- Mechanism and comments
- General coagulation defect.
- Bleeding time normal.
- Decreased synthesis of factors II, VII, IX, X, protein C, protein S.
4
Q
Platelet disorders
A
- Defects in platelet plug formation –> increased bleeding time (BT).
- Platelet abnormalities –> microhemorrhage:
- Petechiae
- Mucous membrane bleeding
- Purpura
- Increased bleeding time
- Possible decreased platelet count (PC)
- Epistaxis
5
Q
Bernard-Soulier syndrome
- Type of disorder
- PC
- BT
- Mechanism
A
- Type of disorder
- Platelet disorder
- PC
- Decreased
- BT
- Increased
- Mechanism
- Defect in platelet plug formation.
- Decreased GpIb –> defect in platelet-to-vWF adhesion.
6
Q
Glanzmann thrombasthenia
- Type of disorder
- PC
- BT
- Mechanism
- Labs
A
- Type of disorder
- Platelet disorder
- PC
- No effect
- BT
- Increased
- Mechanism
- Defect in platelet plug formation.
- Decreased GpIIb/IIIa –> defect in platelet-to-platelet aggregation.
- Labs
- Blood smear shows no platelet clumping.
7
Q
Immune thrombocytopenia
- Type of disorder
- PC
- BT
- Mechanism
- Labs
A
- Type of disorder
- Platelet disorder
- PC
- Decreased
- BT
- Increased
- Mechanism
- Defect: anti-GpIIb/IIIa antibodies –> splenic macrophage consumption of platelet/antibody complex.
- May be triggered by viral illness.
- Decreased platelet survival.
- Defect: anti-GpIIb/IIIa antibodies –> splenic macrophage consumption of platelet/antibody complex.
- Labs
- Increased megakaryocytes on bone marrow biopsy.
8
Q
Thrombotic thrombocytopenic purpura
- Type of disorder
- PC
- BT
- Mechanism
- Pathogenesis
- Labs
- Symptoms
- Treatment
A
- Type of disorder
- Platelet disorder
- PC
- Decreased
- BT
- Increased
- Mechanism
- Inhibition or deficiency of ADAMTS 13 (vWF metalloprotease) –> decreased degradation of vWF multimers.
- Pathogenesis
- Increased large vWF multimers –> increased platelet adhesion –> increased platelet aggregation and thrombosis.
- Decreased platelet survival
- Labs
- Schistocytes, increased LDH.
- Symptoms
- Pentad of neurologic and renal symptoms, fever, thrombocytopenia, and microangiopathic hemolytic anemia.
- Treatment
- Exchange transfusion and steroids.
9
Q
von Willebrand disease
- Type of disorder
- PC
- BT
- PT
- PTT
- Mechanism
- Diagnosis
- Treatment
A
- Type of disorder
- Mixed platelet and coagulation disorder
- PC
- No effect
- BT
- Increased
- PT
- No effect
- PTT
- No effect or increased
- Mechanism
- Intrinsic pathway coagulation defect
- Decreased vWF –> normal or increased PTT
- Depends on severity;
- vWF acts to carry/protect factor VIII
- Defect in platelet plug formation
- Decreased vWF –> defect in platelet-to-vWF adhesion.
- Mild but most common inherited bleeding disorder.
- Autosomal dominant.
- Intrinsic pathway coagulation defect
- Diagnosis
- Diagnosed in most cases by ristocetin cofactor assay
- Decreased agglutination is diagnostic
- Treatment
- DDAVP, which releases vWF stored in endothelium.
10
Q
DIC
- Type of disorder
- PC
- BT
- PT
- PTT
- Mechanism
- Causes
- Labs
A
- Type of disorder
- Mixed platelet and coagulation disorder
- PC
- Decreased
- BT
- Increased
- PT
- Increased
- PTT
- Increased
- Mechanism
- Widespread activation of clotting leads to a deficiency in clotting factors, which creates a bleeding state.
- Causes
- Sepsis (gram-negative), Trauma, Obstetric complications, acute Pancreatitis, Malignancy, Nephrotic syndrome, Transfusion
- STOP Making New Thrombi
- Labs
- Schistocytes, increased fibrin split products (d-dimers), decreased fibrinogen, decreased factors V and VIII.
11
Q
Hereditary thrombosis syndromes leading to hypercoagulability
- Factor V Leiden
- Prothrombin gene mutation
- Antithrombin deficiency
- Protein C or S deficiency
A
- Factor V Leiden
- Production of mutant factor V that is resistant to degradation by activated protein C.
- Most common cause of inherited hypercoagulability in whites.
- Prothrombin gene mutation
- Mutation in 3′ untranslated region –> increased production of prothrombin –> increased plasma levels and venous clots.
- Antithrombin deficiency
- Inherited deficiency of antithrombin: has no direct effect on the PT, PTT, or thrombin time but diminishes the increase in PTT following heparin administration.
- Can also be acquired: renal failure/nephrotic syndrome –> antithrombin loss in urine –> increased factors II and X.
- Protein C or S deficiency
- Decreased ability to inactivate factors V and VIII.
- Increased risk of thrombotic skin necrosis with hemorrhage following administration of warfarin.
- Skin and subcutaneous tissue necrosis after warfarin administration –> think protein C deficiency.
- “Protein C Cancels Coagulation.”
12
Q
Blood transfusion therapy
- Blood transfusion risks
- For each
- Dosage effect
- Clinical use
- Packed RBCs
- Platelets
- Fresh frozen plasma
- Cryoprecipitate
A
- Blood transfusion risks
- Infection transmission (low)
- Transfusion reactions
- Iron overload
- Hypocalcemia (citrate is a calcium chelator)
- Hyperkalemia (RBCs may lyse in old blood units).
- Packed RBCs
- Dosage effect: Increases Hb and O2 carrying capacity
- Clinical use: Acute blood loss, severe anemia
- Platelets
- Dosage effect: Increases platelet count (increase ~5000/mm3/unit)
- Clinical use: Stop significant bleeding (thrombocytopenia, qualitative platelet defects)
- Fresh frozen plasma
- Dosage effect: Increases coagulation factor levels
- Clinical use: DIC, cirrhosis, warfarin overdose, exchange transfusion in TTP/HUS
- Cryoprecipitate
- Dosage effect: Contains fibrinogen, factor VIII, factor XIII, vWF, and fibronectin
- Clinical use: Treat coagulation factor deficiencies involving fibrinogen and factor VIII
13
Q
Leukemia vs. lymphoma
- Leukemia
- Lymphoma
A
- Leukemia
- Lymphoid or myeloid neoplasms with widespread involvement of bone marrow.
- Tumor cells are usually found in peripheral blood.
- Lymphoma
- Discrete tumor masses arising from lymph nodes.
- Presentations often blur definitions.
14
Q
Reactions
- Leukemoid reaction
- CML
A
- Leukemoid reaction
- Acute inflammatory response to infection.
- Increased WBC count with increased neutrophils and neutrophil precursors such as band cells (left shift)
- Increased leukocyte ALP.
- CML
- Also increased WBC count with left shift
- Decreased leukocyte ALP).
15
Q
Hodgkin vs. non‑Hodgkin lymphoma
- Location
- Characteristics
- Age
- Associations
- Constitutional sign / symptoms
A
- Location
-
H: Localized, single group of nodes
- Extranodal rare
- Contiguous spread (stage is strongest predictor of prognosis).
- Prognosis is much better than with non-Hodgkin lymphoma.
-
NH: Multiple, peripheral nodes
- Extranodal involvement common
- Noncontiguous spread
-
H: Localized, single group of nodes
- Characteristics
- H: Characterized by Reed-Sternberg cells
- NH: Majority involve B cells (except those of lymphoblastic T-cell origin)
- Age
-
H: Bimodal distribution
- Young adulthood and > 55 years
- More common in men except for nodular sclerosing type
- NH: Peak incidence for certain subtypes at 20–40 years old
-
H: Bimodal distribution
- Associations
- H: 50% of cases associated with EBV
- NH: May be associated with HIV and immunosuppression
- Constitutional sign / symptoms
- H: Constitutional (“B”) signs/symptoms—low-grade fever, night sweats, weight loss
- NH: Fewer constitutional signs/symptoms
16
Q
Reed-Sternberg cells
- Characteristics
- Prognosis
A
- Characteristics
- Distinctive tumor giant cell seen in Hodgkin disease
- Binucleate or bilobed with the 2 halves as mirror images (“owl eyes” [A]).
- RS cells are CD15+ and CD30+ B-cell origin.
- 2 owl eyes × 15 = 30.
- Nodular sclerosing form most common (affects women and men equally).
- Necessary but not sufficient for a diagnosis of Hodgkin disease.
- Distinctive tumor giant cell seen in Hodgkin disease
- Better prognosis with strong stromal or lymphocytic reaction against RS cells.
- Lymphocyte-rich form has best prognosis.
- Lymphocyte mixed or depleted forms have poor prognosis.
17
Q
Burkitt lymphoma
- Type of condition
- Occurs in…
- Genetics
- Comments
A
- Type of condition
- Non-Hodgkin lymphoma: neoplasm of mature B cells
- Occurs in…
- Adolescents or young adults
- Genetics
- t(8;14)—translocation of c-myc (8) and heavy-chain Ig (14)
- Comments
- “Starry sky” appearance [A], sheets of lymphocytes with interspersed macrophages (arrows).
- Associated with EBV.
- Jaw lesion [B] in endemic form in Africa; pelvis or abdomen in sporadic form.
22
Q
Mycosis fungoides / Sézary syndrome
- Type of condition
- Occurs in…
- Comments
A
- Type of condition
- Non-Hodgkin lymphoma: neoplasm of mature T cells
- Occurs in…
- Adults
- Comments
- Adults present with cutaneous patches [C] / plaques/tumors with potential to spread to lymph nodes and viscera.
- Circulating malignant cells seen in Sézary syndrome.
- Indolent, CD4+.
23
Q
Multiple myeloma
- Definition
- Associated with:
A
- Definition
- Monoclonal plasma cell (“fried egg” appearance) cancer that arises in the marrow and produces large amounts of IgG (55%) or IgA (25%).
- Most common 1° tumor arising within bone in the elderly (> 40–50 years old).
- Numerous plasma cells with “clock face” chromatin and intracytoplasmic inclusions containing immunoglobulin [B].
- Associated with:
- Increased susceptibility to infection
- Primary amyloidosis (AL)
- Punched-out lytic bone lesions on x-ray [A]
- M spike on serum protein electrophoresis
- Ig light chains in urine (Bence Jones protein)
- Rouleaux formation (RBCs stacked like poker chips in blood smear)
-
Think CRRAABBB MMeat:
- hyperCalcemia
- Renal insufficienc
- Rouleaux formation
- Anemia
- primary Amyloidosis
- Bone lytic lesions
- Back pain
- Bence Jones protein
- Monoclonal M protein spike
24
Q
Related to multiple myeloma
- Waldenström macroglobulinemia
- Monoclonal gammopathy of undetermined significance (MGUS)
A
-
Waldenström macroglobulinemia
- M spike = IgM
- –> hyperviscosity symptoms
- No lytic bone lesions.
-
Monoclonal gammopathy of undetermined significance (MGUS)
- Monoclonal expansion of plasma cells with serum monoclonal protein < 3g/dL (“M spike”) and bone marrow with < 10% monoclonal plasma cells.
- Asymptomatic precursor to multiple myeloma.
- Patients with MGUS develop multiple myeloma at a rate of 1–2% per year.
27
Q
Acute lymphoblastic leukemia/lymphoma (ALL)
- Type of condition
- Age
- Characteristics
A
- Type of condition
- Leukemia: lymphoid neoplasm
- Age
- < 15 years
- Characteristics
- T-cell ALL can present as mediastinal mass (leukemic infiltration of the thymus).
- Associated with Down syndrome.
- Peripheral blood and bone marrow have really really increased lymphoblasts [A].
- TdT+ (marker of pre-T and pre-B cells), CD10+ (pre-B cells only).
- Most responsive to therapy.
- May spread to CNS and testes.
- t(12;21) –> better prognosis.
28
Q
Small lymphocytic lymphoma (SLL)/ chronic lymphocytic leukemia (CLL)
- Type of condition
- Age
- Characteristics
A
- Type of condition
- Leukemia: lymphoid neoplasm
- Age
- > 60 years
- Characteristics
- CD20+, CD5+ B-cell neoplasm.
- Often asymptomatic, progresses slowly
- Smudge cells [B] in peripheral blood smear
- Autoimmune hemolytic anemia.
- SLL same as CLL except CLL has increased peripheral blood lymphocytosis or bone marrow involvement.
29
Q
Hairy cell leukemia
- Type of condition
- Age
- Characteristics
- Treatment
A
- Type of condition
- Leukemia: lymphoid neoplasm
- Age
- Adults.
- Characteristics
- Mature B-cell tumor in the elderly.
- Cells have filamentous, hair-like projections [C] .
- Stains TRAP (tartrate-resistant acid phosphatase (+)).
- TRAP stain largely replaced with flow cytometry.
- Causes marrow fibrosis –> dry tap on aspiration.
- Treatment
- Cladribine (2-CDA), an adenosine analog (inhibits adenosine deaminase).
30
Q
Acute myelogenous leukemia (AML)
- Type of condition
- Age
- Characteristics
- Risk factors
A
- Type of condition
- Leukemia: myeloid neoplasm
- Age
- Median onset 65 years
- Characteristics
- Auer rods [D]
- Peroxidase (+) cytoplasmic inclusions seen mostly in M3 AML
- Really really increased circulating myeloblasts on peripheral smear
- t(15;17) –> M3 AML subtype responds to all-trans retinoic acid (vitamin A), inducing differentiation of myeloblasts
- DIC is a common presentation in M3 AML and can be induced by chemotherapy due to release of Auer rods.
- Risk factors
- Prior exposure to alkylating chemotherapy, radiation, myeloproliferative disorders, Down syndrome.
31
Q
Chronic myelogenous leukemia (CML)
- Type of condition
- Age
- Characteristics
- Treatment
A
- Type of condition
- Leukemia: myeloid neoplasm
- Age
- Peak incidence 45–85 years, median age at diagnosis 64 years
- Characteristics
- Defined by the Philadelphia chromosome (t[9;22], bcr-abl)
- Myeloid stem cell proliferation
- Presents with increased neutrophils, metamyelocytes, basophils [E], splenomegaly
- May accelerate and transform to AML or ALL (“blast crisis”).
- Very low leukocyte alkaline phosphatase (LAP) as a result of low activity in mature granulocytes (vs. leukemoid reaction, in which LAP is increased).
- Treatment
- Responds to imatinib (a small-molecule inhibitor of the bcr-abl tyrosine kinase).
33
Q
Langerhans cell histiocytosis
- Definition
- Presentation
A
- Definition
- Proliferative disorders of dendritic (Langerhans) cells from monocyte lineage.
- Cells are functionally immature and do not efficiently stimulate primary T lymphocytes via antigen presentation.
- Cells express S-100 (mesodermal origin) and CD1a.
- Presentation
- Presents in a child as lytic bone lesions [A] and skin rash or as recurrent otitis media with a mass involving the mastoid bone.
- Birbeck granules (“tennis rackets” on EM) are characteristic [B].
35
Q
Polycythemia vera
- Type of disorder
- Definition
- RBCs (increased/decreased)
- WBCs (increased/decreased)
- Platelets (increased/decreased)
- Philadelphia chromosome (+/-)
- JAK2 mutations(+/-)
A
- Type of disorder
- Chronic myeloproliferative disorder
- Definition
- Hematocrit > 55%, somatic (non-hereditary) mutation in JAK2 gene.
- 2° polycythemia is via natural or artificial increases in EPO levels.
- Presentation
- Often presents as intense itching after hot shower.
- Rare but classic symptom is erythromelalgia (severe, burning pain and reddish or bluish coloration) due to episodic blood clots in vessels of the extremities [A].
- RBCs
- Increased
- WBCs
- Increased
- Platelets
- Increased
- Philadelphia chromosome
- (-)
- JAK2 mutations
- (+)
36
Q
Essential thrombocytosis
- Type of disorder
- Definition
- RBCs (increased/decreased)
- WBCs (increased/decreased)
- Platelets (increased/decreased)
- Philadelphia chromosome (+/-)
- JAK2 mutations(+/-)
A
- Type of disorder
- Chronic myeloproliferative disorder
- Definition
- Similar to polycythemia vera, but specific for overproduction of abnormal platelets –> bleeding, thrombosis.
- Bone marrow contains enlarged megakaryocytes [B].
- RBCs
- No effect
- WBCs
- No effect
- Platelets
- Increased
- Philadelphia chromosome
- (-)
- JAK2 mutations
- (+) (30-50%)
37
Q
Myelofibrosis
- Type of disorder
- Definition
- RBCs (increased/decreased)
- WBCs (increased/decreased)
- Platelets (increased/decreased)
- Philadelphia chromosome (+/-)
- JAK2 mutations(+/-)
A
- Type of disorder
- Chronic myeloproliferative disorder
- Definition
- Fibrotic obliteration of bone marrow [C].
-
Teardrop RBCs and immature forms of the myeloid line.
- “Bone marrow is crying because it’s fibrosed.”
- RBCs
- Decreased
- WBCs
- Variable
- Platelets
- Variable
- Philadelphia chromosome
- (-)
- JAK2 mutations
- (+) (30-50%)
