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Hematology pathology, pathologic RBC forms, neoplasm, anemia, coagulation…
Hematology pathology
pathologic RBC forms
degmacyte; bite cell
G6PD deficiency
acanthocyte; spur cell(有棘赤血球)
liver disease, abetalipoproteinemia
basophilic stippling(好塩基斑点)
sideroblastic anemia(鉄芽球性貧血), thalassemias
macro-ovalocyte(巨大卵形細胞)
megaloblastic anemia
elliptocyte(楕円細胞)
hereditary elliptocytosis, usually aymptomatic
echinocyte; burr cell(有棘赤血球)
end-stage renal disease, liver disease, pyruvate kinase deficiency
dacrocyte; teardrop cell(涙滴赤血球)
bone marrow infiltration, thalassemias
spherocyte(球状赤血球)
hereditary spherocytosis, hemolytic anemia
Howell-Jolly body
hyposplenia or asplenia
Heinz body
G6PD deficiency
ringed sideroblast(環状鉄芽球)
sideroblastic anemia
schistocyte(分裂赤血球)
microangiopathic hemolytic anemia, including DIC, TTP, HUS, HELLP syndrome, mechanical hemolysis
sickle cell(鎌状赤血球)
sickle cell anemia
target cell
HbC disease, asplenia, liver disease, thalassemia
neoplasm
multiple myeloma
↑infection, primary amyloidosis, punched out lytic bone lesion, M spike, Ig light chain in urine, Rouleaux formation
numerous plasma cells with ckock-face chromatin and intracytoplasmic inclusions containing immunoglobulin
.>40~50 years old
monoclonal gammopathy of undetermined significance
monoclonal expansion of plasma cells
asymptomatic, may lead to MM
monoclonal plasma cell cancer that arises in the marrow and produces large amount of IgG or IgA
Waldenstrom macroglobulinemia
hyperviscosity sindrome (過粘着性症候群)
chromosomal translocations
t(11;14): Mantle cell lymphoma
t(14;18) follicular lymphoma
t(9;22): CML
t(15;17) APL (type of AML)
t(8;14): Burkitt lymphoma
leukemia
lymphoid neoplasm
chronic lymphocytic leukemia/small lymphocytic lymphoma
age>60 years; adult; CD20+, CD23+, CD5+, Bcell neoplasm
asymptomatic, progress slowly; smudge cell(破損赤血球); autimmune hemolytic anemia
Richter transformation: CLL/SLL transformation into aggressive lymphoma, commonly diffuse large B cell lymphoma
hairy cell leukemia
adult male; mature B cell; filamentous, hair like projection
cause marrow fibrosis→dry tap; massive splenomegaly and pancytopenia
stain TRAP
treatment: cladribine, pentostatin
acute lymphoblastic leukemia/lymphoma
in children; less common in adults; associated with Down syndrome
↑↑↑lymphoblast
TdT+, CD10+
t(12;21)→better prognosis
myeloid neoplasm
acute myelogenous leukemia
65; Auer rods; myeloperoxidase + cytoplasmic inclusion; ↑↑↑circulating myeloblast in peripheral smear
chemotherapy, radiation, myeloproliferative disorders, Down syndrome, t(15;17)
chronic myelogenous leukemia
45-85
defined by Philadelphia chromosome( t(9;22),BCR-ABL) and myeloid stemcell proliferation
neutrophil, metamyelocyte, myelocyte, basophil, splenomegaly, may transform to AML, ALL
treatment: bcr-abl tyrosine kinase inhibitor(eg. imatinib, dasatinib)
unregulated growth and differentiation of WBCs in bone marrow→marrow failure→anemia, infection, hemorrhage
infiltration of liver, spleen, lymph nodes and skin possible
chronic myeloproliferative disorder
essential thrombocythemia
massive proliferation of megakaryocytes and platelet
bleeding and thrombosis
polycythemia vera
primary polycythemia, ↑RBC
erythromelagia, intense itching after hot shower
↓EPO
treatment: phlebotomy, hydoxyurea, ruxolitinib
myelofibrosis
obliteration of bone marrow with fibrosis due to ↑fibroblast activity
often associated withmassive splenomegaly and teardrop RBC
associated with JAK2 mutation
polycythemia
inappropriate absolute
↑EPO; malignancy, hydronephritis
polycythemia vera
↑↑RBC mass; ↓EPO
appropriate absolute
O₂ saturation; lung disease, congenital heart disease, high altitude
relative
↓plasma volume; dehydration, burns
Langerhans cell histocytosis
S-100 and CD1a
Birbeck granules
in child, lytic bone lesion, skin rash, recurrent ostitis media
proliferative disorder of dendritic cells
Hodgkin lymphoma
CD15+ and CD30+ B cell origin
types
nodular sclerosis: most common
lymphocyte rich: best prognosis
mixed cellularity: eosinophilia, immunocompromised
lymphocyte depleted: in immunocompromised
Reed-Sternberg cells: giant, binucleate, owl eyes
myelodysplastic syndrome
Pseudo-Pelger-Huet anomaly: neutrophil with bilobed nuclei
risk of transformation to AML
stem-cell diorder involving ineffective hematopoiesis(瀉血)→defect in cell maturation of nonlymphoid lineage
tumor lysis syndrome
treatment: hydration, allopurinol, rasburicase
hyperkalemia, hyperphosphatemia, hyperuricemia, acute kidney injury
by massive tumor cell lysis, most often in lymphoma/leukemia
leukemia vs lymphoma
leukemia: lymphoid or myeloid neoplasm with widespread involvement of bone marrow, found in peripheral blood
lymphoma: discrete tumor mass arising from lymph node
Hodgkin vs non Hodgkin
Hodgkin
localized and single group of nodes; contiguous spread; better prognosis
Reed-Stermberg cells
bimodal distribution
non-Hodgkin
multiple lymph node involved; extranodal involvement; noncontiguous spread
majority involve B cells
associate with HIV and autoimmune disease
non-Hodgkin lymphoma
neoplasm of B cell
diffuse large B cell lymphoma
children, adult; alteration in Bcl-2, Bcl-6; most common type in adult
follicular lymphoma
t(14,18); painless waxing and waning(増減する) adenopathy
Burkitt lymphoma
adolescents or young adults; t(8;14); Starry sky appearance, sheet of lymphocyte with interspersed macrophage; associated with EBV
mantle cell lymphoma
t(11;14); very aggressive
marginal zone lymphoma
t(11;18); associated with chronic inflammation
primary central nervous system lymphoma
HIV/AIDS; EBV; confusing, memory loss, seizures; ring-enhancing in immunocompromised patient
neoplasm of T cell
mycosis fungoides/Sezary syndrome
skin patch, plaque, CD4 cell with cerebriform nuclei and intraepidermal neoplastic cell
adult Tcell lymphoma
by HTLV
anemia
intrinsic hemolytic anemia
HbC disease
hemoglobin srystal inside RBC, target cell
mutation of β-chain, extravascular necrosis
pyruvate kinase deficiency
↓hemoglobin affinity for O₂
in newborn
AR, pyruvate kinase defect, extravascular hemolysis
G6PD deficiency
↑RBC susceptibility to oxidant stress→hemolytic anemia
back pain, hemoglobinuria, Heinz body and bite cell in blood smear
most common enzymatic disorder, extra-and intravascular hemolysis, XR
paroxysmal nocturnal hemoglobinuria
↑incidence of acute leukemias, associated with aplastic anemia
Coombs - hemolytic anemia, pancytopenia, venous thrombosis
↑mutation in hematopoetic stem cell
treatment: eclizumab
↑complement linking intravascular RBC lysis; mutation in PIGA gene→impaired synthesis of GPI anchor for decay-accelerating factor and membrane inhibitor of reactive lysis that protect RBC membrane from complement)
hereditary spherocytosis(遺伝性球状赤血球症)
small round RBCs→premature removal by spleen
splenomegaly, aplastic crisis
extravascular hemolysis, AD, defect in proteins interacting with RBC membrane skeleton and plasma membrane
treatment: splenectomy
sickle cell anemia
crescent-shaped RBC
complications: aplastic crisis, sutosplenectomy, splenic crisis, Salmonella osteomyelitis, dactylitis, priapism, acute chest syndrome, avascular necrosis, stroke, microhematouria
low O₂, high altitude, acidosis precipitating sickling→anemia, vaso-occlusive disease
HbS point mutation→extra- and intravascular hemolysis
microcytic, hypochromic; MCV<80fL
iron dificiency
fatigue, conjunctival pallor, pica(異食症), spoon nail, glossitis, cheiolosis, Plummer-Vinson syndrome
↓iron, ↑TIBC, ↓ferritin, ↑free erythrocyte protoporphyrin, ↑RDW
↓ iron due to chronic bleeding, malnutrition, absorption disorder, GI surgery, ↑ demand
α-thalassemia
types
α-thalassemia minima: αα/α-, no anemia
α-thalassemia minor: α-/α- or αα/--, mild anemia
hemoglobin H disease: --/α-, moderate to severe
hemoglobin Barts disease: --/--, no α-globin, hydrop fetalis, incompetible with life
α-globin gene deletion→↓α-globin synthesis
β-thalassemia
point mutation in splice site and promoter sequence→↓β-globin synthesis
β-thalassemia minor: β chain is underproduced, usually asymptomatic
β-thalassemia major
β chain is absent→severe microcytic, hypochromic anemia with target cell
require blood transfusion
skeletal deformities, hepatosplenomegaly
HBF, HBA₂(α₂δ₂)
lead poisoning
inhibit ferrochelatase and ALA dehydratase→↓heme synthesis and ↑RBC protoporphyrin
inhibit rRNA degradation→RBC retain aggregates of rRNA
lead line in gingivae and on metaphyses of long bone, encephalopathy and erythrocyte basophilic stippling, abdominal colic(疝痛) and sideroblastic anemia, wrist and foot droping
sideroblastic anemia
ringed sideroblast, basophilic stippling
↑iron, normal or ↓TIBC, ↑ferritin
cause: genetic, acquired, and reversible (eg. alcohol), lead, vitaminB6 deficiency, copper deficiency, etc
normocytic normochromic anemia
increase in LDH, reticulocyte, unconjugated bilirubin, urobilinogen in urine
intravascular hemolysis
↓haptoglobin, ↑schistocyte on blood smear
hemoglobinuria, hemosiderinuria, urobilinogen in urine
↑unconjugated bilirubin
mechanical hemolysis, paroxysmal nocturnal hemoglobinuria, microangiopathic hemolytic anemia
intrinsic vs extrinsic, intravascular vs extravascular
extravascular hemolysis
macrophage in spleen clear RBC
hereditary spherocytosis, AIHA
no hemoglobinuria, hemosiderinuria, urobilinogen in urine
extrinsic hemolytic anemia
autoimmune hemolytic anemia
many are idiopathic
Coombs +
cold(IgM and complement)
triggered by cold
in CLL, mycoplasma pneumoniae infection, infectious mononucleosis
Coombs test
direct
reagent: anti-human globulin
+→agglutination
patient component: anti-Ig antibody added to RBC
indirect
reagent: blood and anti-human globulin
+→agglutination
patient component: serum
warm(IgG)
in SLE, CLL, certain drugs
microangiopathic anemia
seen in DIC, TTP, HUS, SLE, HELLP syndrome, hypertensive emergency
schistocyte
RBCs are damaged when passing through obstructed or narrowed vessel lumina
macroangiopathic anemia
schistocyte
prosthetic heart valve and aortic stenosis
infections
interpretation of iron study
chronic disease: ↓serum iron, ↓transferrin and TIBC, ↑ferritin
hemochromatosis: ↑serum iron, ↓transferrin and TIBC, ↑ferritin, ↑↑transferrin saturation
iron study: ↓serum iron, ↑transferrin and TIBC, ↓ferritin, ↓↓transferrin saturation
pregnancy/OCP use: ↑transferrin and TIBC,
↓transferrin saturation
macrocytic; MCV>100fL
megaloblastic anemia
RBC macrocytosis, hypersegmented neutrophil, glossitis
folate deficiency
no neurologic symptoms
cause: malnutrition, malabsorption, drugs, ↑requirement
maturation of nucleus of precursor cell in bone marrow delayed relative to maturation of cytoplasm
orotic aciduria
AR
children failure to thrive, developmental delay, megaloblastic anemia
inability to convert orotic acid to UMP because of defect in UMP synthase
vitamin B12 deficiency
neurologic symptoms
cause: pernicious anemia(悪性貧血), malabsorption, gastrectomy, insufficient intake
nonmegaloblastic anemia
without hypersegmented neutrophils
diamond-blackfan anemia
defect in erythroid progenitor cells, in children
cause: alcoholism, liver disease
nonhemolytic, normocytic anemia
anemia of chronic disease
rheumatoid arthritis, SLE, neoplastic disorder, chronic kidney disease
↓iron, ↓TIBC, ↑ferritin
inflammation→↑hepcidin (inhibiting iron transport)→↓release of iron from macrophage and ↓iron absorption from gut
aplastic anemia(再生不良性貧血)
due to: radiation, drug, viral agent, Fanconi anemia, idiopathic
↓reticulocyte, ↑EPO, pancytopenia
failure or destruction of myeloid stem cells
hypocellular bone marrow with fatty infiltration; dry tap
fatigue, malaise, pallor, purpura, mucosal bleeding, petechiae, infection
coagulation disorder
platelet disorder
thrombotic thrombocytopenic purpura
inhibition or deficiency of ADAMTS13→↓degradation of vWF multimers→↑platelet aggregation and thrombosis
schistocyte
fever, microangiopathic hemolytic anemia, thrombocytopenia, renal failure, neurologic symptom
glanzmann thrombasthenia(血小板無力症)
defect in platelet integrin (Gp2b/Gp3a)→defect in platelet aggregation
Bernard-Soulier syndrome
defect in platelet plug formation, large platelet
↓Gp1b→defect in platelet to vWF adhesion
hemolytic-uremic syndrome
thrombocytopenia, microangiopathic hemolytic anemia, acute renal failure
commonly in children, shiga-like toxin of EHEC
microhemorrhage, mucous membrane bleeding, epistaxis(鼻血), petechiae, purpura
immune thrombocytopenia
anti Gp2b/3a antibody→splenic macrophage consumption of platelet-antibody complex
treatment: steroid, IVIG, tiruximab, splenectomy
defect in platelet plug formation→↑bleeding time
hemophilia A,B,C
A: factorⅧ, XR
B: factorⅨ, XR
↑PTT
C: factorⅪ, AR
hemarthroses(関節血腫), easy bruising, bleeding after trauma or surgery
treatment: desmopressin(A) + factor
hereditary thrombosis syndrome
factor Ⅴ Leiden
complications: DVT, cerebral vein thromboses, recurrent pregnancy loss
production of mutant factor Ⅴ is resistant to degradation by activted protein C
protein C or S deficiency
↓ ability to inactivate factor Ⅴa and Ⅷa
antithrombin deficiendy
can also caused by renal failure
deficiency of antithrombin: has no direct effect on PT, PTT, thrombin time, but diminish increase in PTT following heparine administration
prothrombin gene mutation
↑ production of prothrombin
lab
PTT: function of common and intrinsic pathway
INR: calculated from PT, 1=normal, >1prolonged
PT: function of common and extrinsic pathway
mixed platelet and coagulation diorders
von Willebrand disease
AD
treatment: desmopressin
defect in platelet plug formation
intrinsic pathway coagulation defect: ↓vWF→↑PTT
disseminated intravascular coagulation; DIC
causes: sepsis, trauma, obsteric complication, acute pancreatitis, malignancy, nephrotic syndrome, transfusion
schistocytes, ↑fibrin degradation product(D-dimer), ↓fibrinogen, ↓factor Ⅴand Ⅷ
clotting→deficiency in clotting factors→bleeding state
vitamin K deficiency
↓activity of factor2,7,9,10, proteinC, proteinS
blood transfusion therapy
fresh frozen plasma/prothrombin complex concentrate
FFP contains all coagulation factors and plasma proteins
PCC contains factor 2,7,9,10 as well as protein C and S
↑coagulation factor level
risk include infection transmission, transfusion reaction, iron overload, hypocalcemia, hyperkalemia
cryoprecipitate: fibrinogen factor8,13, vWF, fibronectin
packed RBC: ↑Hb and O₂ carrying capacity
platelets: ↑platelet count
leukocytopenia
left shift:↑ neutrophil precursors
seen with neutrophilia in the acute response to infection or inflammation
leukoerythroblastic reaction
severe anemia, marrow response
band cell, metamyelocyte
eosinophilia
<30cells/mm³
Cushing syndrome, corticosteroid
neutropenia
sepsis, drugs, aplastic anemia, SLE, radiation
absolute count<1500cells/mm³, severe infection when <500cells/mm³
lymphopenia
HIV, DiGeorge, SCID, SLE, corticosteroid, radiation, sepsis, postoperative
<1500cells/mm³
heme synthesis
iron poisoning
cell death due to peroxidation of membrane lipids
nausea, vomiting, gastric bleeding, lethargy, scarring leading to GI obstruction
high mortality rate with accidental ingestion by children
treatment: chelation and dialysis
disorder
acute intermittent porphyria
porphobilinogen, ALA are accumulated
painful abdomen, port wine, polyneuropathy, psychological disturbance, drug, alcohol, starvation
porphobilinogen deaminase deficiency (AD)
treatment: hemin and glucose
porphyria cutanea tarda
uroporphyrin is accumulated
blistering cutaneous photosensitivity and hyperpigmentation
uroporphyrinogen decarboxylase deficiency (AD)
lead poisoning
protoporphyrin and ALA are accumlated
microcytic anemia, GI and kidney disease, mental deterioration(in child), headache, memory loss, demyelination
ferrochelatase and ALA dehydratase is affected
synthesis
glycine+succinyl CoA→aminolevulinic acid→porphobilinogen→→→protoporphyrin→heme