Hematologic Disorders Flashcards
DDx of clinical findings commonly seen in diabetic retinopathy
anemia/leukemia, vascular occlusive disease, radiation retinopathy, ocular ischemic syndrome, purtcher’s ret etc
totipotent
directed just to blood
pluripotent
directed toward anything in the body
Stem cells differentiate into…
lymphoid or myeloid stem cells
Lymphoid stem cells produce
lymphocytes
Myeloid stem cells produce
Monocytes, RBCs, platelets, neutrophil, eosinophil, basophil
Where are RBCs generated?
red bone marrow in large bones
How long do mature RBCs live?
120 days, then they are recycled by macrophages in the liver and spleen via phagocytosis
What is a heme broken down into?
iron + globulin
What is globulin broken down into?
essential amino acids
What is heme broken down into?
bilirubin, then secreted into gallbladder through liber through digestion then excreted
What releases erythropoietin?
Kidney
What are causes of anemia?
blood loss, hypo-proliferation, hemolytic
What is morphologic anemia?
macrocytic vs normocytic vs microcytic
What are hemoglobin content colors?
red is normochromic and pale is hypochromic
Symptoms of anemia
fatigue/weakness, dizziness, HA, SOB, numbness or coldness in fingers and toes
Signs of anemia
pallor of skin and nails, brittle nails, fast heartbeat, cutaneous hemorrhages, epithelial abnormalities (vascular), lymphadenopathy, bone tenderness, hepatosplenomegaly
Elderly patient have a higher chance of being anemic primarily through
poor nutrition
What is the most common anemia in the US?
iron-deficiency
How is iron deficiency anemia categorized?
microcytic and hypochromic aka inadequate levels of essential compounds causes RBCs to be smaller and pale
Define iron deficiency anemia
inadequate iron levels from chronic recurrent hemorrhage from GI tract and GU tract secondary to dietary deprivation or malabsorption from small intestine
Is iron deficiency anemia more common in men or women
women
Systemic signs and symptoms of iron deficient anemia
HA, light headedness, pica, glossitis, koilonychia, dysphagia
What is koilonychia?
spooning brittle nails
What is dysphagia?
trouble swallowing
Ocular manifestations of iron deficient anemia
conjunctival findings of pallor and hemorrhage; hemorrhage, CWS, exudates, dilated tortuous veins, CRVO with or without macular edema, cranial nerve palsies
Define aplastic anemia
reduction in all cell types from bone marrow
How is aplastic anemia characterized?
normocytic and normochromic
What is the cause of aplastic anemia?
bone marrow dysfunction from unknown origin in >50% of cases or secondary to external chemical or physical agent
What drugs can cause aplastic anemia?
chloramphenicol, acetazolamide and methazolamide
What is acetazolamide used to treat?
angle closure glaucoma and IIH
What is the mortality associated with aplastic anemia?
80%
What is the treatment for aplastic anemia?
bone marrow transplant
Systemic signs and symptoms of aplastic anemia?
aplastic anemia, easy bruisability, epistaxis (nosebleed), increased menstrual flow, bacterial infections of mouth and perirectal area
Ocular signs and symptoms of aplastic anemia?
conjunctival pallor, subconjunctival hemorrhage (recurrent subconj hemes is a sign of anemia), hyphema, retinal findings (hemes, CWS, pallor of ON)
How is pernicious anemia categorized?
macrocytic and normochromic
What is the definition of pernicious anemia?
hereditary autoimmune disorder of the gastric mucosa which leads to absence of intrinsic factor and can’t absorb B12
What is B12 critical for?
synthesis of nucleic acids which are involved in forming blood precursors (RBCs grow without dividing)
Who gets pernicious anemia?
elderly people of northern european ancestry, african americans and latino americans
What is the treatment of pernicious anemia?
vitamin b12 injections
Systemic signs and symptoms of pernicious anemia
glossitis, GI disturbances like atrophic gastritis, anorexia, diarrhea, neurogenic disturbances, autoimmune diseases
Ocular manifestations of pernicious anemia
conjunctival pallor, retinal findings (dilated veins, hemorrhages, pallor of fundus, retinal edema), optic nerve pallor
Treatment of anemias
iron deficient: 200 mg elemental iron (3 tabs daily); aplastic anemia: remove causative agent and receive bone marrow transplant; pernicious anemia 1000 mg IM injection of vit B12 monthly for life
Define thrombocytopenia
destruction of platelets leads to platelet thrombi and tissue hypoxia
What are the types of thrombocytopenia?
TPP and ITP
What is TPP?
thrombocytopenia purpura: hemolytic anemia, non-immune mediated, inherited
What is ITP?
idiopathic thrombocytopenia purpora; hemolytic anemia, antiplatelet antibodies, following viral infections in children and drug exposures in adults
What drugs may cause thrombocytopenia?
quinine, quinidine, sulfonamides, heparin, phenytoin, diazepam, and acetaminophen
Define sickle hemoglobinopathies
inherited disorder with abnormal erythrocyte function; abnormal hemoglobin structure due to substitution of single amino acid
What amino acid may be substituted in sickle cell?
either lysine or glutamate
What is the result of distorted Hb?
decreases RBC O2 transport capability
What is the evolutionary reason for sickle cell?
protects against infection; 10% of AA and 20% of africans
What type of hemoglobin exists after birth?
HbA, tetramer protein with two alpha chains and two beta chains
HbF
normal fetal hemoglobin
HbS
valine for glutamate
HbC
lysine for glutamate
Beta thalassemia
abnormal Hb chain synthesis prevalent in mediterranean countries
HbS + HbS
sickle cell anemia SS, most severe systemic
HbS + HbC
sickle cell C, moderate severity with more severe ophthalmic presentations
HbS + betathal
sickle cell thalassemia, moderate severity and more severe ophthalmic
HbA + HbC
hemoglobin C trait AC
HbA + HbS
sickle cell trait AS; most common
Which sickle cell form is most common?
trait AS, asymptomatic with no anemia
SC and Sthal produce more hyper-viscosity in the blood =
higher prevalence of sickle cell retinopathy
What causes sickling?
stress, viral illness, dehydration, hypoxia, exertion
What are effects of sickling?
obstructive occlusions, microvascular occlusions, hemolysis
What are systemic complications of SCD?
Acute chest syndrome and splenic sequestration crisis
What is acute chest syndrome?
chest pain, coughing, difficulty breathing, fever
What is splenic sequestration crisis?
due to RBCs being trapped within the spleen, leads to hypoxia, thrombosis, infarction and fibrosis; usually manifests between 3 months and 5 years of age, symptoms: abdominal fullness, weakness, pallor, tachycardia, and tachypnea
What systemic manifestations from SCD?
acute sickle-cell crisis, chronic organ damage, non-vaso occlusive
Acute sickle cell crisis
due to vaso-occlusion of microvasculature; extreme pain of back/chest/extremities; complications of CVA, hepatic crisis and renal failure
Chronic organ damage from SCD
skin ulcer, microinfarct of renal medulla (can’t concentrate urine), autospenectomy
Non-vaso occlusions in SCD
increases infections, gallstones, abnormal growth and development
Proliferative sick cell retinopathy
10% of SS and 32% of SC
T/F High VEGF levels in SS are counterbalanced by high level of thrombospondin whereas elevated levels of VEGF in HbSc are unaffected because of low THBS levels
true, THBS counter-acts the VEGF response
Ocular manifestations of SCD
conjunctival sickling, focal iris atrophy, hyphema, increase in IOP, rubeosis irides, optic disc sign, choroidal vascular occlusion
T/F first line of treatment of elevated IOP in sickle cell is CAI
false, contraindicated because CAIs induce a sickling event due to CO2 changing the pH to be more acidic which increases the viscosity of the blood
Is elevated IOP a concern in patients with a hyphema and SCD?
yes
When is IOP concerning for SCD?
> 24 mmHg, ocular emergency, may require anterior chamber washout if hyphema present
Non proliferative SCR
venous tortuosity, black sunbursts, refractile deposits, silver wire arterioles, salmon patch hemorrhages, angiod streaks, CRAO or CRVO, enlarged FAZ
Stage 1 and 2 sickle cell retinopathy
peripheral occlusions, anastomoses between artery and veins in periphery
Stage 3, 4, 5
anastomoses between sea fan neo, hemorrhaging and fibrosis, and tractional detachment
Lab tests for SCD
sickledex tests for HbS; (+) test= turbid blood after shaking in solutions// electrophoresis
Systemic SCD treatment
oxygen supplementation, good nutrition and folic acid supplements, genetic counseling, blood transfusions, bone marrow transplants, hydroxyurea
What is hydroxyurea for?
increases amount of HgF
Treatment for SCD neo
focal ablation, feeder vessel treatment, pan-retinal scatter, anti-VEGF, vitrectomy
Define chronic myeloproliferative disorders
overproduction of any of the formed elements of blood increasing blood viscosity
What is polycythemia vera?
most common myeloproliferative disorder; over production of RBCs
What is Waldenstom’s macroglobulinemia?
myeloproliferative disorder, overproduction of globulin
What are anticardiolipin antibodies?
auto-antibodies against protein-phospholipid complexes; often seen in lupus or RA
What’s a hyper-coagulable state?
causes arterial and venous thrombosis, coronary artery disease, pulmonary HTN
When should you consider antiphospholipid syndrome?
if you see vascular occlusion in young patient
Define leukemia
neoplastic disease of bone marrow; abnormal proliferation of lymphocytes and their precursors
Leukemia is linked to exposure to what medications
benzene, cigarettes, and chemotherapy drugs
Acute lymphocytic leukemia
mostly children under 10, M>F, highly treatable and typically detected early
Acute myeloblastic leukemia
mid aged and elderly, M>F, whites, malignancy of granulocytes, radiation/chemical/hereditary factors, 8 subtypes depending on stage of development of myeloblasts
Chronic lymphocytic leukemia
middle-aged and elderly, 75% of cases after 60 years, WBCs have extended lifespan
Treatment for CLL
suppression of humoral immunity
Treatment of CML
bone marrow transplant
Chronic myeloblastic leukemia
adults > 50, caused by philadelphia chromosome in bone marrow
Systemic manifestations of acute leukemia
failure of normal hematopoiesis, infection, CNS involvement, joint and bone pain
Systemic manifestations of chronic leukemia
asymptomatic early, insidious onset of vague symptoms, disease progression
Ocular manifestations of leukemia
adnexa, lacrimal gland infiltration, EOM infiltration, swelling or subconj heme, exophthalmos, sterile peripheral ulcers with pannus, episcleritis, infiltrates of perivascular regions, secondary angle closure glaucoma, iris color change, pseudohypopyon
What is leukemic retinopathy?
dilated and tortous venules, yellowing of vascular reflex, hemorrhages, retinal infiltrates, roth spots, CWS, micro-As
Opportunistic infection
cytomegalovirus, herpes simplex, herpes zoster ophthalmicus, mumps, toxoplasmosis, bacterial infection, fungal infection
Systemic leukemia management
chemotherapy, radiation, bone marrow transplantation
Ocular management of leukemia
systemic chemotherapy, irradiation and intrathecal chemotherapy, bone marrow transplantation
Ocular side effects to leukemia cytotoxic drug tx
Cataracts, cranial nerve palsy, optic atrophy, intraocular inflammation
Ocular side effects to leukemia bone marrow transplants with chemo
graft vs host; sjogren like dry eye, conjunctival keratinization, ectropion, uveitis
