Coagulation disorders PT PTT

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.

Hemophilia A or B Type of disorder PT PTT Mechanism and comments Treatment

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. Treatment Recombinant factor VIII (in hemophilia A).

Vitamin K deficiency Type of disorder PT PTT Mechanism and comments

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.

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

Bernard-Soulier syndrome Type of disorder PC BT Mechanism

Type of disorder Platelet disorder PC Decreased BT Increased Mechanism Defect in platelet plug formation. Decreased GpIb --\> defect in platelet-to-vWF adhesion.

Glanzmann thrombasthenia Type of disorder PC BT Mechanism Labs

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.

Immune thrombocytopenia Type of disorder PC BT Mechanism Labs

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. Labs Increased megakaryocytes on bone marrow biopsy.

Thrombotic thrombocytopenic purpura Type of disorder PC BT Mechanism Pathogenesis Labs Symptoms Treatment

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.

von Willebrand disease Type of disorder PC BT PT PTT Mechanism Diagnosis Treatment

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. Diagnosis Diagnosed in most cases by ristocetin cofactor assay Decreased agglutination is diagnostic Treatment DDAVP, which releases vWF stored in endothelium.

DIC Type of disorder PC BT PT PTT Mechanism Causes Labs

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 _S_epsis (gram-negative), _T_rauma, _O_bstetric complications, acute _P_ancreatitis, _M_alignancy, _N_ephrotic syndrome, _T_ransfusion _STOP_ _M_aking _N_ew _T_hrombi Labs Schistocytes, increased fibrin split products (d-dimers), decreased fibrinogen, decreased factors V and VIII.

Hereditary thrombosis syndromes leading to hypercoagulability Factor V Leiden Prothrombin gene mutation Antithrombin deficiency Protein C or S deficiency

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_ _C_ancels _C_oagulation.”

Blood transfusion therapy Blood transfusion risks For each Dosage effect Clinical use Packed RBCs Platelets Fresh frozen plasma Cryoprecipitate

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

Leukemia vs. lymphoma Leukemia Lymphoma

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.

Reactions Leukemoid reaction CML

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).

Hodgkin vs. non‑Hodgkin lymphoma Location Characteristics Age Associations Constitutional sign / symptoms

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 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 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

Hematology and Oncology - Pathology (2) Flashcards by Heather Acuff

Coagulation disorders

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.

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Hemophilia A or B

Type of disorder
PT
PTT
Mechanism and comments
Treatment

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.
Treatment
- Recombinant factor VIII (in hemophilia A).

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Vitamin K deficiency

Type of disorder
PT
PTT
Mechanism and comments

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.

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Platelet disorders

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

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Bernard-Soulier syndrome

Type of disorder
PC
BT
Mechanism

Type of disorder
- Platelet disorder
PC
- Decreased
BT
- Increased
Mechanism
- Defect in platelet plug formation.
- Decreased GpIb –> defect in platelet-to-vWF adhesion.

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Glanzmann thrombasthenia

Type of disorder
PC
BT
Mechanism
Labs

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.

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Immune thrombocytopenia

Type of disorder
PC
BT
Mechanism
Labs

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.
Labs
- Increased megakaryocytes on bone marrow biopsy.

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Thrombotic thrombocytopenic purpura

Type of disorder
PC
BT
Mechanism
Pathogenesis
Labs
Symptoms
Treatment

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.

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von Willebrand disease

Type of disorder
PC
BT
PT
PTT
Mechanism
Diagnosis
Treatment

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.
Diagnosis
- Diagnosed in most cases by ristocetin cofactor assay
- Decreased agglutination is diagnostic
Treatment
- DDAVP, which releases vWF stored in endothelium.

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DIC

Type of disorder
PC
BT
PT
PTT
Mechanism
Causes
Labs

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.

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Hereditary thrombosis syndromes leading to hypercoagulability

Factor V Leiden
Prothrombin gene mutation
Antithrombin deficiency
Protein C or S deficiency

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.”

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Blood transfusion therapy

Blood transfusion risks
For each
- Dosage effect
- Clinical use
Packed RBCs
Platelets
Fresh frozen plasma
Cryoprecipitate

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

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Leukemia vs. lymphoma

Leukemia
Lymphoma

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.

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Reactions

Leukemoid reaction
CML

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).

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Hodgkin vs. non‑Hodgkin lymphoma

Location
Characteristics
Age
Associations
Constitutional sign / symptoms

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
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
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

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Reed-Sternberg cells

Characteristics
Prognosis

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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.
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.

Burkitt lymphoma

Type of condition
Occurs in…
Genetics
Comments

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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.

Diffuse large B-cell lymphoma

Type of condition
Occurs in…
Genetics
Comments

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Type of condition
- Non-Hodgkin lymphoma: neoplasm of mature B cells
Occurs in…
- Usually older adults, but 20% in children
Genetics
- t(14;18)
Comments
- Most common type of non-Hodgkin lymphoma in adults.

Mantle cell lymphoma

Type of condition
Occurs in…
Genetics
Comments

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Type of condition
- Non-Hodgkin lymphoma: neoplasm of mature B cells
Occurs in…
- Older males
Genetics
- t(11;14)—translocation of cyclin D1 (11) and heavy-chain Ig (14)
Comments
- CD5+.

Follicular lymphoma

Type of condition
Occurs in…
Genetics
Comments

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Type of condition
- Non-Hodgkin lymphoma: neoplasm of mature B cells
Occurs in…
- Adults
Genetics
- t(14;18)—translocation of heavy-chain Ig (14) and bcl-2 (18)
Comments
- Indolent course; bcl-2 inhibits apoptosis.
- Presents with painless “waxing and waning” lymphadenopathy.

Adult T-cell lymphoma

Type of condition
Occurs in…
Genetics
Comments

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Type of condition
- Non-Hodgkin lymphoma: neoplasm of mature T cells
Occurs in…
- Adults
Genetics
- Caused by HTLV-1 (associated with IV drug abuse)
Comments
- Adults present with cutaneous lesions
  - Especially affects populations in Japan, West Africa, and the Caribbean.
- Lytic bone lesions, hypercalcemia.

Mycosis fungoides / Sézary syndrome

Type of condition
Occurs in…
Comments

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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+.

Multiple myeloma

Definition
Associated with:

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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

Related to multiple myeloma

Waldenström macroglobulinemia
Monoclonal gammopathy of undetermined significance (MGUS)

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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.

Myelodysplastic syndromes * Definition * Pseudo–Pelger-Huet anomaly

* Definition * Stem cell disorders involving ineffective hematopoiesis --\> defects in cell maturation of all non-lymphoid lineages. * Caused by de novo mutations or environmental exposure (e.g., radiation, benzene, chemotherapy). * Risk of transformation to AML. * **Pseudo–Pelger-Huet anomaly** * Neutrophils with bilobed nuclei (two nuclear masses connected with a thin filament of chromatin) typically seen after chemotherapy.

Leukemias

* Unregulated growth of leukocytes in bone marrow * --\> increased or decreased number of circulating leukocytes in blood and marrow failure * --\> anemia (decreased RBCs), infections (decreased mature WBCs), and hemorrhage (decreased platelets) * Leukemic cell infiltrates in liver, spleen, and lymph nodes are possible.

Acute lymphoblastic leukemia/lymphoma (ALL) * Type of condition * Age * Characteristics

* 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.

Small lymphocytic lymphoma (SLL)/ chronic lymphocytic leukemia (CLL) * Type of condition * Age * Characteristics

* 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.

Hairy cell leukemia * Type of condition * Age * Characteristics * Treatment

* 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).

Acute myelogenous leukemia (AML) * Type of condition * Age * Characteristics * Risk factors

* 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.

Chronic myelogenous leukemia (CML) * Type of condition * Age * Characteristics * Treatment

* 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).

Disorders associated with these chromosomal translocations * t(9;22) * t(8;14) * t(11;14) * t(14;18) * t(15;17)

* t(9;22) (**_Philadelphia_** chromosome) * **_CML_** (bcr-abl hybrid) * **_Philadelphia_** **_C_**rea**_ML_** cheese. * t(8;14) * Burkitt lymphoma (c-myc activation) * t(11;14) * Mantle cell lymphoma (cyclin D1 activation) * t(14;18) * Follicular lymphomas (bcl-2 activation) * Diffuse large B-cell lymphoma * t(15;17) * M3 type of AML (responsive to all-trans retinoic acid)

Langerhans cell histiocytosis * Definition * Presentation

* 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].

Chronic myeloproliferative disorders * Definition * Disorders

* Definition * The myeloproliferative disorders represent an often-overlapping spectrum * JAK2 is involved in hematopoietic growth factor signaling. * Mutations are implicated in myeloproliferative disorders other than CML. * Disorders * Polycythemia vera * Essential thrombocytosis * Myelofibrosis * CML

Polycythemia vera * Type of disorder * Definition * RBCs (increased/decreased) * WBCs (increased/decreased) * Platelets (increased/decreased) * Philadelphia chromosome (+/-) * JAK2 mutations(+/-)

* 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 * (+)

Essential thrombocytosis * Type of disorder * Definition * RBCs (increased/decreased) * WBCs (increased/decreased) * Platelets (increased/decreased) * Philadelphia chromosome (+/-) * JAK2 mutations(+/-)

* 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%)

Myelofibrosis * Type of disorder * Definition * RBCs (increased/decreased) * WBCs (increased/decreased) * Platelets (increased/decreased) * Philadelphia chromosome (+/-) * JAK2 mutations(+/-)

* 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%)

CML * Type of disorder * Definition * Treatment * RBCs (increased/decreased) * WBCs (increased/decreased) * Platelets (increased/decreased) * Philadelphia chromosome (+/-) * JAK2 mutations(+/-)

* Type of disorder * Chronic myeloproliferative disorder * Definition * bcr-abl transformation leads to increased cell division and inhibition of apoptosis. * Treatment * Imatinib (Gleevec). * RBCs * Decreased * WBCs * Increased * Platelets * Increased * Philadelphia chromosome * (+) * JAK2 mutations * (-)

Polycythemia * For each * Plasma volume (increased/decreased) * RBC mass (increased/decreased) * O2 saturation (increased/decreased) * EPO levels (increased/decreased) * Associations * Relative * Appropriate absolute * Inappropriate absolute * Polycythemia vera

* Relative * _Plasma volume_: Decreased * _RBC mass_: No effect * _O2 saturation_: No effect * _EPO levels_: No effect * _Associations_: decreased plasma volume (dehydration, burns). * Appropriate absolute * _Plasma volume_: No effect * _RBC mass_: Increased * _O2 saturation_: Decreased * _EPO levels_: Increased * _Associations_: Lung disease, congenital heart disease, high altitude. * Inappropriate absolute * _Plasma volume_: No effect * _RBC mass_: Increased * _O2 saturation_: No effect * _EPO levels_: Increased * _Associations_: Renal cell carcinoma, Wilms tumor, cyst, hepatocellular carcinoma, hydronephrosis. * Due to ectopic EPO. * Polycythemia vera * _Plasma volume_: Increased * _RBC mass_: Really increased * _O2 saturation_: No effect * _EPO levels_: Decreased * _Associations_: Due to negative feedback.

Hematology and Oncology - Pathology (2) Flashcards

(39 cards)