Anemia: Diminished Erythropoiesis - Aplastic Anemia Flashcards
MCC of anemia among hospitalized patients in the US?
Anemia of chronic disease → systemic inflammation
In general, what is anemia of chronic disease?
- systemic inflammation
- reduced proliferation of erythroid progenitors
- impaired iron utilization (it is there, just can’t be used)
3 categories of chronic illnesses that cause anemia
- chronic microbial infection
- chronic immune disorders
- neoplasms
3 examples of chronic microbial infections that may → anemia
- osteomyelitis
- bacterial endocarditis
- lung abscess
Which neoplasms may lead to anemia?
- lung/breast carcinoma
- Hodgkin’s
Which chronic immune disorders may lead to anemia?
- RA
- regional enteritis
Anemia resulting from chronic disease is similar to which type of anemia?
iron deficiency anemia
lab findings for anemia of chronic disease
- ⇡ stored Fe
- ⇣ Fe
- ⇡serum ferritin
- ⇣ total iron-binding capacity
(do NOT give oral Fe, but EPO can help)
Anemia of chronic disease pathogenesis: due to persistent systemic inflammation →
iron sequestration → IL-6 = increased hepatic hepcidin synthesis
(results in decreased absorption & hematopoiesis; progenitors can’t use the iron)
How does iron sequestration help the body fight infection?
keeps it from microbes that might also need it to survive (ex: H. flu)
(hepcidin = structurally similar to defensins)
Anemia of chronic disease: tx
- underlying causes
- EPO
Define aplastic anemia
Chronic primary hematopoietic failure and pancytopenia (no RBC, WBC, or platelets)
4 Causes of aplastic anemia
- Autoimmune
- Chemical / drug exposure
- Viral infection
- Whole body radiation
Define fanconi anemia
Rare AR disorder caused by inherited defects in DNA repair complex → hypofunctioning marrow early in life
(also have other congenital anomalies)
Congenital anomalies seen with fanconi anemia
- Hyperplasia of kidney and spleen
- Bone anomalies → thumbs of radii
10-15% of adult-onset aplastic anemia is due to _____
inherited telomerase defects or abnormally short telomerases
Inherited telomerase defects → ______(2)
- premature hematopoietic stem cell exhaustion
- marrow aplasia
2 major etiologies of aplastic anemia (pathogenesis)
- T-cell suppression of hematopoietic stem cells
- fundamental stem cell abnormality
T-cell suppression of hematopoietic stem cells that leads to aplastic anemia is caused by _______.
Stem cell antigenically altered by drug exposure, infection, etc → killing of progenitors
(apoptotic pathways upregulated by IFN-g)
Karyotypic abnormalities may transform aplastic anemia into _____ or _____.
- myeloid neoplasms
- AML
If ______ is present, it is NOT aplastic anemia
splenomegaly
Aplastic anemia has an insidious onset and initial findings depend on ______.
which cell line is affected first
(eventually → pancytopenia)
Signs of thrombocytopenia (2)
- petechiae
- ecchymoses
Anema: s/sx (3)
- progressive weakness
- pallor
- dyspnea
Neutropenia s/sx (2)
- persistent minor infections
- sudden onset or chills/fever/prostration
Bone marrow biopsy of a patient with aplastic anemia will show _____; whereas myeloid neoplasms will show _____.
- very hypocellular marrow
- hypercellular marrow
Viral causes of aplastic anemia (3)
- CMV
- EBV
- Herpes Zoster (Varicella)
Chemical agents that may cause aplastic anemia (5)
- Alkylating agents
- Antimetabolites
- Benzene
- Chloramphenicol
- Inorganic arsenicals
5 Idiosyncratic causes of aplastic anemia
- Carbamazepine
- Gold salts
- Mesantoin
- Phenylbutazone
- Penicillamine
“Dry tap”
marrow aspirates w/little material
(better to do a marrow biopsy)
In addition to hypocellular bone marrow, aplastic anemia may show _____ (morphological findings)
- granulocytopenia
- thrombocytopenia → mucocutaneous bacterial infections, abnormal bleeding
If aplastic anemia patients need multiple transfusions, this could lead to _____.
hemosiderosis
aplastic anemia tx : _____ or _____.
- bone marrow transplant
- immunosuppressive tx (if no donor or they are too old)
(Blood transfusion if progressing)
Morphology unique to myelophthisic anemia (2)
- Teardrop red cells (aka Dacrocytes) : due to tortuous escape from fibrotic marrow
- Leukoerythroblastosis: abnormal release of RBC precursors and immature granulocytes
Myelophthisic anemia is a form of bone marrow failure where _____ replace normal marrow.
space-occupying lesions
In myelophthisic anemia space-occupying lesions replace normal bone marrow leading to
- Distortion
- Fibrosis
- Disturbed the egress of WBC/RBC
Most common cause of myelophthisic anemia
metastatic cancer
(usually breast, lung or prostate; can be any marrow infiltrative process i.e. granulomatous disease)
How does chronic renal failure lead to anemia (3)?
- Decreased renal EPO synthesis → decreased RBC production
- Extracorpuscular defect reduces RBC lifespan
- Platelet dysfunction → Iron deficiency
Treatment of anemia in chronic renal failure
EPO + iron
Hepatocellular liver disease can be associated with macrocytic anemia due to ______
decreased marrow function
(toxic, infectious or cirrhotic)
Liver failure causes lipid abnormalities → RBC membrane to acquire _____ in the blood.
phospholipids/cholesterol
Hypothyroidism can cause a mild _____ anemia
normochromic, normocytic
