Hematology Flashcards
Anemia
2 SD below normal for age/sex
Hgb concentration <11g/dL for both male and females aged 6 mo - 5 yrs
Labs for anemia
CBC w/ diffferential
peripheral blood smear
reticulocyte count
Reticulocyte results
high- bone marrow working
low- trouble
normocytic, normochromic anemia
anemia of chronic disease
microcytic, hypochromic anemia
IDA
thalassemia
lead intoxication
Macrocytic anemia
vitamine b12
folate deficiency
S/sx of anemia
acute: lethargic, tachy, pallor; infants - irritable, poor oral intake
chronic: may present w/ few or no sx at all
Other findings w/ anemia
jaundice gallstone disease petechiae purpura ecchmosis bleeding
Types of bone marrow failure
fanconi anemia
acquired aplastic anemia
What is fanconi anemia
inherited bone marrow failure syndrome
auto recessive
defective DNA repair
majority develop in first 10 years of life
Clinical manifestation of fanconi anemia
progressive panctyopenia abnormal pigmentation short stature skeletal malformation increased incidence of malignancies
Lab findings for fanconi
thrombocytopenia or leukopenia (then followed by anemia)
anemia = severe aplastic anemia
bone marrow hypoplasia or aplasia
Fanconi anemia may be misdiagnosed as
ITP
Tx for fanconi
supportive
HSCT
Prognosis for fanconi
many succumb to bleeding, infection, or malignancy in adolescence or early adult
high risk for developing Myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
Acquired aplastic anemia
peripheral pancytopenia w/ a hypocellular bone marrow
idiopathic (50%)
meds, toxic exposure (insecticides) and viruses (mono, hepatitis, HIV)
S/sx of acquired aplastic anemia
weakness, fatigue, pallor
frequent or severe infections
purpura, petechiae, bleeding
Lab findings for acquired aplastic anemia
anemia, usually normocytic
low WBC w/ marked neutropenia
thrombocytopenia
low reticulocyte count (bone marrow suppressed)
Complications of acquired aplastic anemia
overwhelming infection
severe hemorrhage
can lead to death
Tx for acquired aplastic anemia
supportive referral stop offending agent abx if infection RBC transfusion for severe anemia Platelet transfusions immunosuppressant agents HSCT
Most common nutritional deficiency in children
Iron deficiency
Prevalence of IDA
1-2 yo
females of chldbearing age
african american and hispanics
poverty
S/sx of IDA
varies w/ severity pallor fatigue, irritability delayed motor dev. hx of Pica (eating ice)
Screening for IDA
12 months- determine Hb concentration and assessment of risk factors
Risk for IDA
low SE status
premature/LBW
lead exposure
exclusive breast feeding beyond 3 mo of age w/o iron supplementation
weaning to whole milk or foods w/o iron
feeding problems, poor growth, inadequate nutrition
Lab findings for IDA
microcytic, hypochromic
Hb <11 g/dL
Ferritin <12 mcg/L
Tx for IDA
Hb 10-11 mg/dL @ 12 mo screening– monitor closely or empirically treated; recheck Hb in one month
ID/IDA: iron 6 mg/kg/d, 3 divided daily doses
Cobalamin
vitamin B12
Causes of b12 deficiency
malabsorption
dietary insufficiency
Folic acid deficiency
increased folate requirement (rapid growth, chronic hemolytic anemia)
malabsorptive syndromes
inadequate dietary intake (rare)
Medications
S/sx of megaloblastic anemia
pallor
glossitis
B12 sx
paresthesias, weakness, unstead gait
decreased vibratory sensation and proprioception on enuro exam
neuro sx only occur w/ B12 not folate
Neuro sx
B12 deficiency
Lab findings for megaloblastic anemia
elevated MCV/MCH
low levels of folic acid or vit B12
neutrophils large and hypersegmented nuclei
Macro-ovalocytes (large, ocal RBC)
Elevated Methylamlonic acid w/ 12
Elevated homocysteine w/ B12 and folate deficiency
How to tell the difference between B12 and folate?
Methylmalonic acid elevated in B12
Hypersegmented nuclei
megaloblastic anemia
Tx for megaloblastic anemia
Vit B12 and/or folic acid supplementation
**tx w/ folate will fix anemia picture in B12 BUT…must treat vit B12 to avoid neuro deficits
Congenital hemolytic anemias
hereditary spherocytosis (HS) thalassemia sickle cell disease G6PD Lead poisoning
Hereditary Spherocytosis (HS)
red cell membrane defect
hemolytic anemia (jaundice, SPLENOMEGALY, gallstones)
Spherocytes*
Increased osmotic fragility*
Tx for HS
supportive +/- RBC transfusion
SPLENECTOMY
Test for HS
osmotic fragility test
Thalassemia
alpha or beta
related to # of gene deletions
microcytic, hypochromic anemia
IRON OVERLOAD
Dx of thalassemia
HgB electrophoresis
Tx for thalassemia
supportive +/- RBC transfusion
Iron monitoring + chelation
splectomy may help
HSCT (severe beta-thal)
Sickle Cell disease sx
Sickle-shaped RBC when deoxygenated Vaso-occlusion that leads to pain! chronic hemolysis splenomegaly splenic infarcts (functional asplenia) Increased risk of bacterial sepsis may see growth failure and delayed puberty
Dx for sickle cell disease
HgB electrophoresis shows HbS
Howell-jolly bodies; target cells on peripheral smear
Tx of sickle cell
avoid precipitating factors
supportive
hydroxyurea*** - depress bone marrow function; used to decrease incidence of pain crises
Stem cell transplant
G6PD deficiency
red cell enzyme defect that causes hemolytic anemia
x-linked recessive
african, mediterranean, asian
episodic hemolysis at times of exposure to:
- oxidant stress of infection
- certain drugs/food substances
Clinical manifestations of G6PD deficiency
neonatal jaundice, hyperbilirubinemia
episodic hemolysis: pallor, jaundice, hemoglobinuria
Lab findings of G6PD
peripheral smear: rate bites; heinz bodies (denatured Hgb)
Heinz bodies
G6PD
Tx for G6PD
supportive
avoid certain foods/drugs known to trigger hemolysis
Etiology of lead poisoning
older home w/ lead pain
Sx of lead poisoning
anemia that is mild, hemolytic and normocytic
Dx of lead poisoning
basophilic stippling
Tx for lead poisoning
chelation
Congenital erythrocytosis aka
familial polycythemia
What is familial polycythemia?
only RBC affected
increased HgB as high as 27 g/dL
Sx of polycythemia
plethora and splenomegaly
h/a, lethargy
Tx for familial polycythemia
phlebotomy
Secondary polycythemia cause
occurs in response to hypoexmia
- cyanotic congenital heart disease
- chronic pulmonary disease (CF)
Tx of secondary polycythemia
correct underlying disorder
phlebotomy when indicated
Tests for bleeding disorders
CBC peripheral smear PT/INT, aPTT \+/- bleeding time Platelet count (N: 150k-400k)
Risk of spontaneous bleeding platelet level
<20k
PT (prothrombin time)
extrinsic and common pathway
I, II, V, VII*, X + TF
PTT/aPTT (activated partial thromboplastin time)
intrinsic and common
I, II, V, VIII, IX, X, XI*, XII
Common pathway factors
I, II, V, X
intrinsic factors
VIII, IX, XI, XII
Extrinsic factors
VII and TF
Prothrombin
II
Thrombin
IIa
Fibrinogen
I
INR
more accurate reflection of PT
used to monitor warfarin
Bleeding time
measure of time for hemostasis
screen test for platelet dysfunction
prolonged in platelet disorder (von Willebrand disease) and severe thrombocytopenia
most common bleeding disorder of childhood
idiopathic thrombocytopenic purpura (ITP)
ITP epidemiology
2-5 yo often follows infection w/viruses immune-mediated 90% have spontaneou remission 10-20% chronic
Pathophys behind ITP
immune-mediated attac against its own platelets (autoantibody bind platelet–> platelets phagocytized primarily by splenic macrophages –> decreased platelet life span)
Clinical manifestations of ITP
petechiae
ecchymosis
epistaxis
Lab findings for ITP
thrombocytopenia
normal WBC
normal Hgb (unless hemorrhage)
PT and aPTT are normal
Dx of ITP
exclusion of others
Tx for ITP
observation in asymptomatiic children avoid medications that compromise platelet function bleeding precautions PREDNISONE IVIG Splenectomy
Inherited bleeding disorders
Von Willebrand disease
Hemophilia
Most common inherited bleeding disorder
Von Willebrand Disease
von willebrand disease
auto dominant
M=F
decrease in the level or impairment in the action of vWF
Most common type of von willebrand disease
Type 1
vWF
bind to factor VIII and is a cofactor for platelet adhesion to the endothelium
Clinical presentation of VWD
prolonged bleeding from mucosal surfaces (epistaxis, menorrhagia, GI)
easy bruising
Lab findings for VWD
normal PT
prolonged or normal aPTT
normal or decreased vWF
PROLONGED BLEEDING TIME (helps differentiate from hemophilia)
Difference between VWD and hemophilia
VWD has prolonged bleeding time
Tx for VWD
desmopressin (DDAVP)
vWF replacement therapy
DDAVP
causes release of vWF and factor VIII from endothelial stores
Hemophilia A
factor VIII deficiency (most common)
Hemophilia B
factor IX deficiency (Christmas disease)
Clinical presentation of hemophilia
bleeding from impaired hemostasis
mild: bleed in response to injury/trauma or surgery; may not be clinically apparent til later in life
severe: spontaneous bleeding, earlier age
bleeding can occur anywhere -- into joints and mm. is common spontaneous hemarthrosis (severe disease) - can lead to joint destruciton if recurrent
Lab findings for hemophilia
normal platelet count, PT and bleeding time
prolonged aPTT (normal in mild disease)
normal vWF
Tx for hemophilia
DDAVP (hemo A) factor replacement (VIII and IX)
Inherited bleeding disorders
VWD
Hemophilia
Acquired bleeding disorders
Disseminated Intravascular Coagulation (DIC)
Liver Disease
Kidney Disease
DIC cause
triggered by event: sepsis, trauma or tissue injury, malignancies
What is DIC
hemorrhage and microvascular thrombosis
Pathophys behind DIC
triger –> widespread activation of coagulation cascade leading to microthrombi –> massive consumption of platelets, fibrin and coagulation factors –> severe bleeding
s/sx of DIC
shock- end organ dysfunction
diffuse bleeding tendency (hematuria, melena, purpura, petechiae; persistent oozing from punctures)
evidence of thrombotic lesion (major vessel thrombosis, purpura fulminans)
lab findings for DIC
decreased platelet count
prolonged aPTT and PT
decreased fibrinogen level (may be normal until late in course)
Elevated D-Dimer and fibrin degradation products (FDPs)
Tx for DIC
identify and treat triggering event
replacement therapy for consumptive coagulopathy
anticoagulant therapy when indicated
Liver synthesizes
prothrombin, fibrinogen
Factors V, VII, IX, X, XII, XIII
Vitamin K dependent factors
II, VII, IX, X
Lab findings for liver disease/vit K def.
platelet count: normal in vitamin K deficiency; normal/low in liver disease
Prolonged PT, aPTT
Tx for liver disease and vit K
treat underlying condition
vitamin K at birth
Inherited thrombotic disorders
Protein C def
Protein S def
antithrombin def
factor V Leiden Mutation
Protein C def
homo and hetero forms
activated protein C inactivated activated factors V and VIII
Warfarin induced skin necrosis
associated w/ protein C def
Protein S def
homo and hetero forms
Protein S is a cofactor for protein C
Factor V Leiden Mutation
point mutation in factor V that leads to resistance to inactivation by activated protein C
hetero and homo forms
Risk with factor V Leiden mutation
increased risk of VTE 2-7x
35 fold with hetero taking oral contraceptives
80 fold in homo
Antithrombin
inhibits thrombin
Clinical presentation of antithrombin def
VTE (efficiency of heparin may be diminished)
Tx of thrombotic disorders
anticoagulant prophylaxis
(UFH, LMWH, warfarin)
1st episode VTE - anticoag for at least 3 mo; may need longer
Type of vasculitis
Henoch-Schonlein Purpura (HSP)
most common type of small vessel vasculitis
HSP
Epidemiology of HSP
boys, ages 2-7
spring and fall
URI often precedes diagnosis
Cause of HSP
deposition of IgA immune complexes in small vessels of the skin, GI tract and kidneys
Clinical presentation of HSP
PALPABLE PURPURA
arthritis/arthralgias
abdominal pain
renal disease
Labs for HSP
normal/elevated platelet count antistreptolysin O (ASO) titer elevated serum IgA may be elevated hemoccult + urinalysis: hematuria, sometimes proteinuria
Tx for HSP
supportive
prognosis generally good
