Heme Flashcards
Hemolytic Uremic Syndrome
-caused by shiga toxin producing bacteria (EHEC, shigella)
-features: prior bloody diarrheal illness, hemolytic anemia with schistocytes, thrombocytopenia (low platelets), acute kidney injury
-normal coagulation studies
Toxin damages capillaries, leading to platelet activation and formation of microemboli, that shear RBCs and cause schistocytes.
Causes low haptoglobin.
Dec. hemoglobin and platelet count.
Inc. lactate dehydrogenase, unconjugated bili, BUN, and creatinine.
Schistocytes
- fragmented RBCs
- diagnostic of a traumatic mechanism and indicate either microangiopathic hemolytic anemia (ex. HUS, TTP, DIC) or mechanical damage
Microangiopathic Hemolytic Anemia
-mechanism: formation of fibrin (protein) mesh in vessels that physically cuts the RBCs
-causes RBC schistocytes
-ex. HUS, DIC, TTP
May have dec. platelets due to micro vascular thrombi formation
Pernicious Anemia
- often due to B12 deficiency/lack of intrinsic factor
- fewer but larger RBCs
- antibodies to intrinsic factor
Effects of CO Poisoning
- inc. carboxyhemoglobin (HbCO)
- no change in paO2 (amount of dissolved oxygen in plasma)
- dec. O2 content and O2 carrying capacity
Von Willebrand Disease
- most common inherited bleeding disorder
- autosomal dominant
- variable penetrance
- absence of von willebrand factor causes impaired platelet function and coagulation issues due to dec. factor VIII activity
- inc. PTT (may be unaffected) and inc. bleeding time
Hemophilia A
- x linked
- deficiency of factor 8
- prolonged PTT
Hemophilia B
- x linked
- deficiency of factor IX
- prolonged PTT
Vitamin K
- required for factors II, VII, IX, and X
- prolonged PT and PTT
T-ALL
- most often in teenagers
- immature T cells migrate to thymus and cause mass
- acute
Chronic Lymphoid Leukemia
- chronic
- lymph cells- B cells
- smudge cell (ruptured fragile B cells on microscopy)
- generalized lymph adenopathy (small lymphocytic lymphoma)
- can lead to diffuse B cell lymphoma (actual mass of B cells in lymph node)
- hypogammaglobulinemia (too few antibodies)
- dysfunctional antibodies cause autoimmune hemolytic anemia (they attack RBCs)
Granulocytes
- eosinophil
- neutrophil
- basophil
- mast cell
Polycythemia Vera
- Myeloproliferative disorder with uncontrolled erythrocyte production (RBC cancer)
- inc. in all cell lines but esp. erythrocytes (high hematocrit, low EPO)
- JAK2 mutation (non receptor tyrosine kinase associated with the erythropoietin receptor)
- pruritis when hot
- inc. bone marrow sensitivity to growth factors
- tx: blood letting
Methemoglobinemia
- dusky discoloration of skin
- unable to carry oxygen
- partial pressure of O2 (P02) will remain unchanged (measure of dissoved O2 and unrelated to hemoglobin)
- can be caused by poisoning with nitrites, drugs
Carbon monoxide affects hemoglobin by:
Competitively binding to heme.
Von Willebrand Disease
Autosomal dominant. Causes impaired platelet adhesion with exposed dcollagen. VW also acts as a carrier for factor VIII.
Prolonged PTT and bleeding time.
Sx: heavy periods, and nose bleeds.
Haptoglobin
Binds free hemoglobin and thus haptoglobin is decreased when there is RBC damage.
Rouleaux Cells
- stacked RBCs
- think multiple myeloma
Basophilic Stippling
- reticulocytosis or lead poisoning
- cytoplasmic remnants of RNA
Howell Jolly Bodies
- remnants of nuclear chromatin
- severe anemia or pts without spleen
Ring Sideroblast
- iron trapped in mitochondria
- form ring around nucleus
- seen in sideroblastic anemia
- seen in bone marrow not peripheral blood smear
Heinz Bodies
- denatured hemoglobin (unstable heme like in H disease thalassemia)
- can be seen in G-6-PD deficiency (African and Mediterranean type)
- visualized with supravital stains (methylene blue, crystal violet)
- eaten by macrophages to form bite cells
Causes of Microcytic Anemia (
- iron deficiency
- thalassemia
- anemia of chronic dz
- siderblastic anemia
- lead poisoning
Causes of Macrocytic Anemia (>100 fL/cell)
- megaloblastic anemia (B12 def, folate def)
- alcoholic liver dz (neutrophils 3-5 on peripheral blood smear)
Causes of Normocytic Anemia with low Reticulocyte Count
- marrow failure
- aplastic anemia
- myelofibrosis
- leukemia/metastasis
- renal failure
- anemia of chronic disease
- should be inc. erythrocytes in anemia (check bone marrow)
Causes of Normocytic Anemia with High Reticulocyte Count
- sickle cell
- G6PD deficiency
- hereditary spherocytosis
- autoimmune hemolytic anemia
- paroxysmal nocturnal hemoglobinuria
Fe Deficiency Anemia
- dec MCV
- dec MCHC
- dec. RDW
- inc. free erythrocyte protoporphyrin (FEP)
- oral apithelial atrophy if Plummer Vinson syndrome present
- koilonychia (spoon nails)
- pica (eating stuff)
Sideroblastic Anemia
- lead poisoning
- B6 deficiency (drug like isoniazid)
- alcoholism
- myelodisplastic syndrome
- ringed sideroblasts present in bone marrow
- body has adequate iron but unable to incorporate it
HbF
- fetal hemoglobin contains y globulin (gamma)
- composed of 2a and 2y (gamma) chains
- babies with B thalassemia do not present at birth due to y globulin
- made in fetus not embryo
Which cells are tdt +?
-immature lymphcytes
CD5 + CD 19 or 20?
-B chronic lymphocytic leukemia cells
CD11c or CD 25 or CD 103 with CD19/20?
- hairy cell leukemia
- dry tap with big spleen
Burkitts
- starry sky (macrophages eating tumor)
- African kid with jaw mass or AIDS pts
- t(8;14) cMYC to immunoglobulin heavy chain juxtaposition
Mantel Cell
- B cell lymphoma
- mantel zone B lymphocytes (CD 5, 19, 20 +, CD23-)
- t(11;14) CCD1 (cyclin D 1 protein)
MALToma
- chronic inflammation (H. pylori, Hashimoto, sjogren) to MALToma
- lymphoma
Multiple Myeloma
- bone marrow tumor
- inc. serum protein with normal albumin
- M spike on serum electophoresis (most common is IgG or IgA)
- rouleax cells
- lytic bone lesions = bone pain, hypercalcemia, bone fracture
- Bence Jones proteins are light chains filtered into urine
Monoclonal Gammopathy of Undetermined Significance
-M spike with no bone lytic lesions or pain (as seen in multiple myeloma)
-may progress to multiple myeloma
-
Adult T Cell Lymphoma
- see in Japan and Caribbean
- T cell tumor
- skin lesions
- lymph involvement
- hypercalcemia
- hyperlobated 4 leaf clover appearance
Reed Sternberg Markers
-CD15+, CD30+, CD45-
t(12;21)
- ALL
- good prognosis with this translocation
Auer Rods
-characteristic of Acute Promyelogenous Leukemia
Stain positive for myeloperoxidase.
Indicate myeloid lineage.
What cancer can be treated with vitamin A?
- PML
- t(15;17)
- auer rods
- fusion of PML/RARA
- RARA is vit A receptor and high vit A helps mature the cancer cells
Essential Thrombocythemia
- inc in all cell lines but esp. thrombocythemia
- JAK2 mutation
Myelofibrosis
- marrow fibrosis secondary to factors released from megakaryocytes
- splenomegly
- dry tap
- biopsy: myelofibrosis and myosis
- tear drop RBCs
- JAK2 mutation
- distinguish from hair cell leukemia and aplastic anemia
Transferrin is (blank) in states of low iron.
Increased.
Labs for Vitamin B12 Deficiency
High homocysteine and high methylmalonic
Labs expected for folate deficiency.
Just inc. homocysteine, and normal methylmalonic acid.
Uremic Platelet Dysfunction
- inc. bleeding time with normal coagulation studies and normal platelet count
- due to significant renal dysfunction due to accumulation of uremic toxins in circulation that impair platelet aggregation and adhesion
- improved with dialysis
Hereditary Spherocytosis
- red cell cytoskeleton abnormalities
- likely defect in spectrin or ankyrin
- inc. osmotic fragility on acidified glycerol lysis testing confirms diagnosis
- sx: hemolytic anemia, jaundice, splenomegaly
- complications: pigmented gallstones and aplastic crises from parvovirus B19
Henoch Schonlein Purpura
- systemic hypersensitivity dz that produces leukoclastic angiitis in small vessels of the dermis and GI tract
- purpuric rash, abdominal pain, and polyarthralgia
- may cause acute glomerulonephritis
- boys aged 3-11
- associated with IgA and C3 deposition
Paroxysmal Nocturnal Hemoglobinuria
-hemolytic anemia, hemoglobinuria which may be nocturnal
-thrombosis
Hypercoagulability
-pancytopenia
-complement mediated cell lysis
-chronic lysis may lead to hemosiderosis of kidney (iron deposition)
-mutated PIGA gene that helps attach many cell surface proteins (CD55, CD59) that inactivate complement
Erythrocytosis
- inc. in erythrocyte production
- this can be due to a left shift in the O2 dissociation curve, leading to hypoxia in the kidney, and inc. EPO synthesis
Glanzmann Thrombasthenia
-deficient GP2b3a
Acanthocytes
Irregular projections on RBCs, typical in abetalipoproteinemia
Bite Cells
When spleen removes Heinz bodies. Due to glucose six phosphate dehydrogenase causing oxidant induced damage.
Tear Drop Cells
Due to myelofibrosis. When marrow is fibrotic, cells must squeeze through.
Hematocrit
-proportion of total blood volume that is composed of RBCs
Thrombotic Thrombocytopenic Purpura
- dec. ADAMT13 leads to large vWF multimers
- pentad of fever, neurologic sx, kidney disease, microangiopathic hemolytic anemia, and thrombocytopenia, although not all pts have neuro sx or fever
- is a primary thrombotic microangiopathy
- thombi in arteriolar microvasculature, causing dec. platelets and schistocytes
- tx: plasma exchange therarpy
How to Identify Reticulocytes
- immature RBC
- larger and bluer than mature RBC
- lacks nucleus
- retains ribosomal RNA
- appears blue on Wright-Giemsa Stain
Pure Red Cell Aplasia
- rare form of marrow failure
- severe hypoplasia of marrow erythroid elements with normal granulopoiesis and thrombopoiesis
- ass. with thymoma, lymphocytic leukemias, and parvovirus B19
Immune Thrombocytopenic Purpura
- immune mediated consumption of platelets
- low platelet count and petechiae
- inc. platelet cell production in bone marrow (not production issue)
Sickle Cell Mutation
- single nucleotide mutation on the B-globin gene
- glutamic acid to valine
- in low O2 concentrations, causes polymerization of HbS itself
B12 Deficiency Signs
- elevated MMA and homocysteine are characteristic
- megaloblastic anemia
- pernicious anemia (previous autoimmune disease likely)
Factor V Leyden Deficiency
- most common cause of hereditary hypercoagulability
- factor V that is resistant to degradation by activated protein C
- leads to inc. clotting
Antithrombin Deficiency
- no direct effect on PT, PTT, or thrombin time
- diminishes inc. in PTT following heparin administration
- can also be acquired in nephrotic syndrome if lost in urine
Protein C or S Deficiency
- dec. ability to inactivate factors Va and and VIIIa
- inc. risk of thrombotic skin necrosis w/ hemorrhage following admin of warfarin
- C Cancels Coagulation
- protein C and S prevent coagulation
Hemoglobin A1 vs A2
- hemoglobin A= 2 alpha 2 beta
- hemoglobin A2= 2 alpha and 2 delta chains
Glucose 6 Phosphate Dehydrogenase Deficiency
- X linked recessive
- more common in people of Mediterranean or African origin
- may protect against malaria
- rate limiting enzyme in production of NADPH
- may be exacerbated by drugs, food (fava beans), or illness
Prussian Blue Stain
- identifies hemosiderin (iron overload)
- hemosiderin is typically seen in kupffer cells in liver
- hemosiderin laden macrophages = siderophages
