RBC Flashcards
4 causes of Heinz bodies
G6PD Deficiency
NADPH Deficiency
Oxidant drug-induced
Unstable hemoglobin variants
Thalassemia
Chronic liver disease
Hyposplenia/asplenia
Chemical induced
See on Supravital staining
Denatured hemoglobin
Pathophys of G6PD deficiency
G6PD normally restores NADPH levels which maintains levels of reduced glutathione in RBCs. Glutathione protects RBCs from oxidative damage. In G6PD deficiency, glutathione levels are depleted and so RBC are vulnerable to oxidizing agents.
Hexo-monophosphate pathway (PK is glycolytic pathway)
Reasons to initiate transfusions in a child with thalssemia
- Symptomatic anemia- fatigue, cardiopulmonary compromise, pHTN
- Delayed growth/no sexual characteristics
- Extramedullary hematopoiesis (cord compression, pathologic #, bone pain from tumor, symptomatic splenomegaly)
- Frequent hemolytic crises
- Thrombosis/stroke
Others:
leg ulcers
Poor school peformance/QoL
Name 4 causes of pure red cell aplasia
· Parvovirus B19 (virus binds to blood group p antigen)
· Thymoma
· Lymphoproliferative disorder (esp. LGL, CLL, MM)
· MDS
Solid tumors, breast, lung renal
· Autoimmune (hypothyroidism)
· Transient erythroblastopenia of childhood
· Drugs (rhEPO, post myeloablative chemotherapy eg busulphan, melphalan)
Meds that are contraindicated in G6PD deficiency; Inheritance pattern.
X-linked
Sulfamethoxazole-Trimethoprim.
Dapsone
Urate oxidase-rasburicase
Methylene blue
Nitrofurantoin
Ciprofloxacin
3 causes of a dual population on blood film in an anemic patient
Recently transfused microcytic/macrocytic anemic patient
Treated Iron Deficiency Anemia or any nutritional deficiency
Erythropoietin Therapy → reticulocytosis
MDS/RARS
Hemolytic processes involving a reticulocyte response
Mixed nutritional deficiency
Name 3 positive results of treating patients with SCD with HU
Reduced frequency of pain episodes
Reduced frequency of ACS
Reduced transfusions in adults with Hb SS
Increases HbF levels
Reduced mortality without an increased risk of malignancy
Chains that make up the following hemoglobins: Gower 1, Gower2, Portland, HgF, Hg A, HgA2.
Hb Gower 1 zeta2 epsilon2
Hb Portland zeta2 gamma2
Hb Gower 2 alpha2 epsilon2
Hb F alpha2 gamma2
Hb A alpha2 beta2
Hb A2 alpha2 delta2
Next to each of the following, write whether the patient has “a comparable” phenotype to HbSS by writing “sickler” or “non-sickler”.
Hb SC:
Hb beta0thal/S:
Hb SD:
Hb beta+thal/S:
Hb SLepore:
HbS-HPFH:
Hb SC: Sickler
Hb beta0thal/S: Sickler
Hb SD (Punjab): Sickler
Hb beta+thal/S: Sickler
Hb SLepore: Sickler
HbS-HPFH: No (if homo HPFH will not sickling, but if heter will sickling)
HbSO(arab) = sickler
HbES =Sickler (HgEbeta thal does hemolyze)
Name 2 hemolytic disorders associated with enzyme deficiencies. Describe the morphological changes for each
G6PD Deficiency: Heinz Bodies, bite cells, blister cells
PK Deficiency: Echinocytes, reticulocytosis (esp. after splenectomy), nRBCs, anisopoikilocytosis
Pathophys of PK deficiency.
Abnormality of glycolytic pathway (Embden-Meyerhof pathway) –> leads to decrease in ATP–>The lack of ATP disturbs the cation gradient across the erythrocytic cell membrane, causing the loss of potassium and water, which results in cell dehydration, contraction, and crenation (echinocytes) and leads to premature destruction of the erythrocyte. –> decreased deformability and hemolysis
Smear: (echinocytes or “prickle cells”), reticulocytosis (esp. after splenectomy), nRBCs, anisopoikilocytosis
AR, gene is PKLR gene
*high level of 2,3-diphosphoglycerate (2,3-DPG) increases the patient’s exercise tolerance by causing a rightward shift in the hemoglobin-oxygen dissociation curve.
Name 4 ways to decrease the complications of IV iron administration.
Provide test dose prior to full dose administration
Pretreatment with steroids
Slow infusion
Avoid high molecular weight dextran
Lower doses of Iron vs Dilution
Tylenol following administration
Avoid in patients with hx of rxn to IV Fe or severe allergy/asthma
Consider avoiding in setting of active infection.
Name 4 causes of refractory iron deficiency anemia
Active H. Pylori
Celiac Disease:
Autoimmune gastritis
Hereditary Iron-refractory iron deficiency anemia (IRIDA) = AR due to TMPRSS6 gene mutation (causes high hepcidin)
Ongoing bleeding
Non compliant
Inadequate iron dose
Mechanism and treatment for post-renal Tx polycythemia.
MOA- ?RAS dysregulation occurs @ 8-24 months post renal Tx. (Hg >170 or hct >51 x 6 mos)
Hormones involved in pathogenesis: RAS, EPO, IGF-1, androgens
Treatment
1. ACEi/ARB
2. Phlebotomy if >180 ( if >180 (or Hct>0.55), target 0.5.. unlike PV 0.45)
3. Native kidney nephrectomy (if elevated EPO)
Causes for high hepcidin
hepcidin HIGH → BLOCKS ferriportin = less iron in circulation
- Increased iron stores (non-pathological)
- inflammation/infection (TNFa , IL6)
- IRIDA due to TMPRSS6 mutation
- Iron replacement (transfusions, PO, IV)
- CKD
Causes for low hepcidin
hepcidin LOW → OPENS ferriportin =more iron in circulation
- Fe deficiency
- Hereditary hemochromatosis
- Increased erythroferrone - will be increased in any state of ineffective erythropoiesis ie Thalassemia
- ESA’s
- Liver disease
- Etoh
- HCV
- Estrogen and Testosterone
“sex, drugs and rock and roll (Iron Maiden)”
Non HFE gene mutations in HH
- hemojuvelin (low hepcidin)
2.hepcidin (loss of function)
3.ferroportin (classical: unable to export iron from macrophages, nonclassical: unable to bind hepcidin) - transferrin receptor (low hepcidin)
HFE (H63D, C282Y, S65C)
What are four proteins in the RBC membrane?
What are three disorders associated with cytoskeletal RBC defects?
- Ankyrin
- Band 3
- Alpha-spectrin
- Beta spectrin
- Protein 4.2
- Protein 4.1.
- Glyocophorin C
HE, HS, HPP, Southeast Asian Ovalocytosis
Causes of microcytosis aside from iron deficiency and hemoglobinopathy?
- LEAD poisioning
- Inherited sideroblastic anemia
- Cu deficiency
4 Zn excess
5.Anemia of chronic inflammation
6 Acquired sideroblastic disorder
-EtOH
-Lead poisoning
-Zn excess
-Cu def
-Drugs: INH, linezolid, chloramphenicol, cycloserine
Pearson syndrome - MDS with acquired thalassemia
- Pediatric Hereditary Elliptocytosis –> 2ry to fragments
What condition produces a “Hg F” only pattern on newborn screening?
Beta thal major!
Child with abrupt normocytic anemia, reticulocytopenia, N H & P and then spontaneous recovery with brisk reticulocytosis. What is the diagnosis?
Transient erythroblastopenia of childhood.
IgG Ab against erythroblasts.
Consequences of iron def in pregnancy?
- postpartum depression
- poor maternal-infant behavioral interaction
- impaired lactation
- low birth weight
- premature delivery
- intrauterine growth retardation
- increased fetal and neonatal mortality.
Recommended daily dose of elemental iron in pregnancy
30mg
(can give concurrently with Vitamin C to increase absorption)
Consider IV iron only after week 13
What is the generic name for monofer? Why is iron absorption increased?
- Ferric carboxymaltose, one-time infusion of 1,000 mg
2.Greater binding of the carbohydrate moiety to iron
What TSat should prompt screening for HH in women and men? What is the most commonly identified HFE gene mutation and which ethnicity is this seen most commonly in?
First repeat fasting! Then if still elevated:
- 0.50 men, 0.45 women
- C282Y (60-90%)
- Northern European, mainly male