Heme Flashcards
1
Q
Hemophilia
A
X-linked recessive inheritance clotting factor disorder
- Hemophilia A: factor VIII decrease → “Aight”
- Hemophilia B: decreased clotting factor IX
- Normal Factor Activity: 50-150%
- mild: 6-49% (Bleeding during surgery)
- moderate: 1-5% (occasional bleeding)
- Severe: <1% (spontaneous bleeding)
-
S/sxs:
-
hemarthrosis (bleeding in joint)
- main sxs = excessive bleeding
-
hemarthrosis (bleeding in joint)
-
Diagnosis: increased PTT, normal PT, normal platelets and function
- → corrected with mixing study
- if PTT is NOT corrected with mixing studies = indication of lupus anticoagulant or factor inhibitor
- most specific test: functional assay for factor VIII or IX
- → corrected with mixing study
-
Tx: replacement for depleted factors
- avoid situations that cause bleeding
- avoid certain drugs that interfere with platelet function (NSAIDs and aspirin)
2
Q
Von Willebrand Disease
A
Autosomal Dominant → most common genetic bleeding disorder clotting factor disorder
- missing protein for platelet function (usually hangs out in the endothelium of the blood vessels and is important for factor VIII transport → platelets cannot adhere to vessel at site of injury → bleeding doesn’t stop as quickly as it should
- hormonal changes, stress, pregnancy, inflammation, and infection can stimulate vWF production
- S/sxs: hx and family hx of bleeding, bruising easily, increased menstrual bleeding, no hemarthrosis, petechiae, bleeding with minor injury
-
Dx:
- decreased vWF and decreased Factor VIII
- normal CBC, normal platelet count, and increased bleeding time
- → normal or prolonged PTT with normal PT
-
Tx: DDVAP (desmopressin)
- if excessive bleeding → transfusion of concentrated blood clotting factors containing vWF
3
Q
Vitamin K Deficiency
A
Clotting Factor Disorder
Vitamin K does not cross the placenta and it is a fat soluble vitamin for bone calcification and activation of coagulation factors
- Vitamin K activates: factors II, VII (half-life = 4-6 hours), IX, X, Protein C and Protein S
- prolonged PT
- causes: malnutrition, abx, fat malabsorption, hemorrhagic disease of the newborn
-
S/sxs:
- bleeding, mucosal bleeding, epistaxis, GI hemorrhage, menorrhagia, and hematuria
-
Dx:
- prolonged PT or elevated INR that improves with phytonadione (generic name for vitamin K1)
- Tx: Oral or SQ phytonadione
4
Q
What causes a high aPTT?
A
activated partial thromboplastin time
measures the intrinsic pathway (slower)
- Intrinsic Pathway Factors: XII, XI, IX, VIII
- aPTT is the time in seconds for a fibrin clot to form: measures the function of factors VIII, IX, and XI
-
Causes of a high aPTT:
- heparin
- decreased factor (VIII, IX, XI), vitamin K, liver disease
- consumption: inhibitor, DIC
5
Q
What causes a high PT?
A
Prothrombin Time: measured in INR
measures the extrinsic pathway (faster pathway)
-
PT is the time in seconds for the fibrin clot to form: measures the function of tissue factor and Factor VII
- Warfarin
- NOACS
- decreased factors: VII, liver disease, Vitamin K
- overconsumption: DIC
6
Q
Heparin-Induced Thrombocytopenia
A
hypercoagulable state
- ≥ 50% reduction in platelet count within 7-10 days of exposure to heparin; results in global thrombocytopenia and thromboembolism due to immune rxn with platelet factor
- S/sxs: hx of multiple DVTs, CBC is normal, PT and PTT is normal
- Dx: HIT assay
-
Tx:
- to prevent thrombotic stroke or MI use antiplatelet therapy: aspirin, clopidogrel, prasugrel or dipyridamole/aspirin combo
- stop the heparin but still need an anticoagulant → must use a direct thrombin inhibitor (dabigatran)
7
Q
Antiphospholipid Syndrome
A
Hypercoagulable State
Dx & Tx trick: CardiB goes to War → Cardiolipin, anti-beta 2, tx with warfarin
certain membrane phospholipids are normally prevented from activating the coagulation cascade by binding to circulating phospholipid-binding proteins; antibodies to these binding proteins block this protective measure and predispose the pt to thrombosis → associated with lupus and PREVIOUS MISCARRIAGES
-
S/sxs:
- hx of multiple DVTs
- CBC is normal, PT and PTT are normal
- hx of multiple DVTs
-
Dx: ANA and CRP in SLE
- Russell’s Viper Venom time is specific to detect lupus anticoagulant
- (+) anticardiolipin antibody
- (+) anti-beta 2 glycoprotein I ELISA
-
Tx:
- Prednisone (for Lupus) and Warfarin
8
Q
Factor V Leiden Mutation
A
Most common genetic hypercoagulable state
mutations in factor V (of the common pathway) make it resistant to normal inactivation by activated protein C and predispose the pt to venous thrombosis
- have high suspicion in pts with recurrent thromboembolic events, thromboembolism in young pts, or in pts with NO risk factors; previous miscarriages
- S/sxs: hx of multiple DVTs, CBC is normal, PT and PTT are normal
-
Dx:
- Factor V leiden Assay
- Protein CC
-
Tx: anticoagulation
- antiplatelet therapy: aspirin, clopidogrel, prasugrel or dipyridamole/aspirin
- oral anticoagulant: Vitamin K antagonist, warfarin, direct thrombin inhibitor (dabigatran) or factor Xa blocker (rivaroxaban)
9
Q
Normal Platelet Range
A
130-400K
10
Q
Idiopathic Thrombocytopenic Purpura
A
aka immune thrombocytic purpura
- Epidemiology: autoimmune rxn to platelets usually after a viral illness → splenic platelet destruction often after an acute infx
- Caused by: viral infx, SLE, lymphoma, medications
-
s/sxs:
- mucosal bleeding, purpura, rashes, easy ecchymosis, petechial rashes
- chronic in adults, self-limiting in children (usually)
-
dx:
- diagnosis of exclusion (clinical diagnosis)
- isolated thrombocytopenia (very low) with a normal CBC and normal peripheral blood smear
- (+) Direct Coombs Test
- Normal PT and aPTT
- Primary ITP: isolated thrombocytopenia (<100K) without a known cause
- Secondary ITP: isolated thrombocytopenia (<100K) with an underlying condition (e.g. HIV)
-
Tx:
- steroids (prednisone) → blocks production of antibody
- IVIG (IV Immune globulin)
- Rituxan (Rituximab) → thrombopoietin receptor agonist
- Splenectomy → reserved for pts with severe thrombocytopenia (<15K)
11
Q
Thrombotic Thrombocytopenic Purpura
A
acute febrile disease with multi-organ thrombosis
-
caused by: deficiency or inhibition of metalloproteinase ADAMTS13 → most commonly disabled by autoantibody
- ADAMTS13 normally degrades (cuts up) vWF multimers; so with deficiency have increased platelet adhesion → platelet thrombosis = damages brain and kidneys
- Triggers: after drugs: quinidine, cyclosporine, clopidogrel, ticlopidine
- Risk Factors: female, AA, use of desmopressin (DDVAP), pregnancy
- Hemolytic uremic syndrome
-
S/sxs:
- adults = purpura and FAT RN → Fever, anemia, thrombocytopenia, renal failure, neurological symptoms
-
Dx: CBC = normal, except LOW platelets
- schistocytes (RBC fragments on the smear)
- (-) Direct Coombs Test
-
Tx:
- plasmapheresis (plasma exchange) = tx of choice → done daily until evidence of subsiding disease and is indicated by a normal platelet count
- corticosteroids + Rituximab (thrombopoietin receptor agonist)
12
Q
Disseminated Intravascular Coagulation
A
abnormal activation of the coagulation sequence lead to the formation of microthrombi through the microcirculation → causes increased consumption of platelets, fibrin, and coagulation factor
-
S/sxs: bleeding and thrombosis occur simultaneously
- bleeding and oozing at catheter sites, mucosal surfaces, petechiae, and ecchymosis, hypotension, and tachycardia
-
Dx:
-
decreased platelets (slightly), increased bleeding time, increased PT and aPTT, (+) D-Dimer
- SCHISTOCYTES
- Fibrinogen = decreased
-
decreased platelets (slightly), increased bleeding time, increased PT and aPTT, (+) D-Dimer
-
Tx:
- supportive care: cryoprecipitate, FFP, platelet transfusions if <10K, heparin for thrombosis, tx the cause
13
Q
A
Schistocyte
14
Q
Microcytic Anemia
A
Low MCV (<80): a Tic is small (microcytic)
- Thalassemia
- Iron Deficiency
- Chronic Disease
- Lead poisoning
15
Q
Iron Deficiency Anemia Pathophys, Etiology, & Risk Factors
A
Microcytic Anemia: most common cause of anemia worldwide
- Pathophys: decreased RBC production due of lack of iron and decreased iron stores (ferritin) normally stored in the bone marrow, liver and spleen
-
Etiology:
- chronic blood loss = most common cause in the US, excessive menstruation, occult GI blood loss, decreased absorption: diet, celiac, bariatric surgery, H.pylori
-
Risk Factors:
- increased metabolic requirements → children, pregnant and lactating women
- → cow milk ingestion in young children: infants fed cow’s milk <1 yr of age, toddlers fed large quantities of cow’s milk
16
Q
Iron Deficiency Anemia S/sxs, PE, Dx, & Tx
A
Microcytic (<80) anemia
-
S/sxs: weakness, fatigue, exercise intolerance, dyspnea
- pagophagia→ craving for ice
- Pica: appetite for non-foods (clay, starch)
-
PE: koilonychia: spooning of the nails
- angular cheilitis : inflammation of the corner of the mouth
- tachycardia, glossitis (smooth tongue), signs of anemia (pallor)
-
Dx:
- CBC: microcytic hypochromic anemia = CLASSIC
- Increased RDW, decreased reticulocytes
- Iron Studies: decreased ferritin (pathognomonic), increased TIBC (transferrin), decreased transferrin saturation
- CBC: microcytic hypochromic anemia = CLASSIC
-
Tx: iron replacement: results in increased reticulocytes (within 5-10days), correction of anemia (6-8weeks), repletion of iron stores (1-3 months)
- increased absorption: take iron replacement with vitamin C (ascorbic acid) with water or orange juice on an empty stomach
- severe life threatening anemia tx: rbc transfusion (e.g.myocardial ischemia)
17
Q
Intrinsic vs Extrinsic Hemolytic Anemia
A
-
Intrinsic: (inherited Disorders)
- sickle cell anemia, thalassemia (microcytic), G6PD deficiency, hereditary spherocytosis
-
Extrinsic: (Acquired Disorders)
- autoimmune hemolytic anemia, DIC, TTP, HUS, paroxysmal nocturnal hemoglobinuria, hypersplenism
18
Q
Hemolytic Anemia S/sxs & Dx
A
- acute onset of pallor from anemia
-
splenomegaly
- jaundice with high indirect bilirubin → too much RBC breakdown for the liver to keep up with
-
splenomegaly
- increased LDH: hemolytic anemias will have increased LDH b/c it is part of the RBC membrane
- increased reticulocytes
-
Dx:
- positive Coombs test if autoimmune etiology
-
G6PD deficiency:
- episodic hemolytic anemia associated with sulfa drugs, fava beans, infx
- HEINZ BODIES
-
Hereditary Spherocytosis:
- (+) osmotic fragility test: mixes RBCs with varying saline, abnormally shaped RBCs will be fragile and fall apart
- Thalassemia: very low MCV + normal TIBC and ferritin
- Sickle Cell Anemia: very high reticulocyte count + pain
19
Q
Autoimmune Hemolytic Anemia Tx
A
1st line = steroids; more severe and persistent may need a splenectomy and/or blood transfusions
20
Q
Hereditary Spherocytosis Tx
A
Hemolytic anemia
splenectomy after appropriate IZs
21
Q
Two types of Autoimmune Hemolytic Anemia
A
-
warm antibody type: autoantibodies attach to and destroy RBCs at temperatures equal to or in excess of normal body temp
- medications: penicillins, cephalosporins, rifampin
-
Cold antibody Type: autoantibodies become most active and attack RBCs only at temperatures below normal body temp
- IgM antibodies
22
Q
Anemia of Chronic Disease Etiology &
Pathophys
A
Microcytic or Normocytic Anemia
due to decreased RBC production in setting of chronic disease
- Etiology: chronic infection, inflammation, autoimmune disorders, malignancy
-
Pathophys: 3 main factors that decrease serum iron:
- increased hepcidin: acute phase reactant that blocks the release of iron from macrophages, blunts EPO, and reduces GI absorption
- increased ferritin: acute phase reactant that sequesters iron into storage
- erythropoietin inhibition via cytokines
23
Q
Anemia of Chronic Disease common causes, Dx, & Tx
A
Microcytic or Normocytic Anemia
-
Most common causes:
- CKD (stage 4 and 5), anemia from connective tissue disorders, other diseases → RA, SLE, HIV, CA, cirrhosis, chronic infx
-
Dx: normocytic or decreased MCV
- decreased TIBC, and normal or increased ferritin
- CBC, serum iron, ferritin, transferrin
-
Tx:
- tx the underlying disorder
- recombinant EPO and iron supplements if HGB <10gm/dl → need to stop once hgb >11 gm/dl due to increased risk of MI and stroke
24
Q
Aplastic Anemia
A
Normocytic, normochromic anemia
- only anemia where all 3 cell lines are decreased: decreased WBCs, decreased RBCs, decreased platelets
- ***will have normal MCV, decreased reticulocytes***
-
Etiology:
- often idiopathic but can be caused by chemicals, drugs, or radiation → ACE inhibitors, sulfonamides, phenytoin, chloramphenicol, chemo, methimazole, and radiation
-
PE: severe pallor, petechiae, ecchymosis, mucosal bleeding
- → severe infx with decreased RBCs, WBCs, and platelets but no reticulocytosis
-
Dx: suspect in pts with pancytopenia (WBC < 1500, ****platelets <50K****)
- decreased reticulocytes (helps to differentiate aplastic anemia in sickle cell patients who usually have a high baseline reticulocyte count)
- serum iron = elevated
- Most accurate test = bone marrow biopsy → normal cell morphology, hypocellular bone marrow with fatty infiltrate
-
Tx:
- d/c offending drug, RBC transfusion
- curative = bone marrow transplant (for pts <50 yo)
- immunosuppression agents for pts >50 yo or with comorbidities
-
Filgrastim (hematopoietic growth factor: G-CSF)
- reduces infx but does not change the course of the disease
25
Folate Deficiency Anemia Etiology
Megaloblastic Macrocytic Anemia
_Folate needed for DNA synthesis_: decreased folate → abnormal synthesis of DNA, **folate stores last 2-4 months**
* _Etiology_: most common: inadequate intake (**alcohols, unbalanced diet**)
* → increased requirements: **pregnancy, infancy, hemolytic anemias, psoriasis** (increased skin turnover)
* → impaired absorption: *celiac disease, inflammatory bowel disease, chronic diarrhea, anticonvulsants* (phenytoin, phenobarbital, carbamazepine)
* → impaired metabolism: **methotrexate, trimethoprim**
* → Loss: dialysis
26
Folate Deficiency Anemia S/sxs, Dx, & Tx
Megaloblastic Macrocytic (\>100) Anemia
* _S/sxs_: anemia sxs **similar to B12 deficiency but _without neurologic abnormalities_**
* fatigue, exercise intolerance, pallor, **chlorosis** (pale, faintly green complexion)
* Glossitis, aphthous ulcers, diarrhea
* Maternal Deficiency = risk of neural tube birth defects
* _Dx_: decreased Folate, increased MCV
* what to order: **CBC, serum vitamin B12, and folate**
* _CBC with peripheral smear_:
* **increased MCV +** megaloblastic anemia **(hypersegmented neutrophils, macroovalocytes)**, low reticulocytes
* **_decreased serum folate (\<3)_**, increased LDH, increased homocysteine, *normal methylmalonic acid* (distinguishes from B12 deficiency)
* _Tx_:
* folate supplements (oral folic acid): **400-1000 micrograms PO daily**
* d/c offending med and limit alcohol consumption
* CDC recommendation and pregnancy: 4000 mcg each day 1 month before becoming pregnant, and during 1st 3 months of pregnancy
27
Vitamin B12 Deficiency Anemia Pathophys and Etiology
Sources of B12: mainly animal products (meats, eggs, dairy)
* _Absorption_: B12 is released by the acidity of the stomach & _combines with_ **intrinsic factor** where it is mainly absorbed in the ***distal ileum***
* _Pathophys_: B12 deficiency → **abnormal synthesis of DNA** ; B12 normally needed to convert homocysteine to methionine for DNA synthesis.
* _Etiology_:
* **Pernicious Anemia = most common cause →** lack of intrinsic factor due to parietal cell antibodies leading to gastric atrophy (_parietal cells secrete acid and intrinsic factor_)
* **Crohn's Disease**, **gastric bypass,** chronic alcohol use, celiac disease, pancreatic insufficiency
* Meds: **H2 blockers, PPIs** (decreased acidity of stomach = less absorption); **metformin** (decreased nucleic acid synthesis)
* **Vegans → decreased intake**
28
Vitamin B12 Deficiency Anemia S/sxs, Dx, & Tx
Megaloblastic macrocytic (\>100) anemia
* _S/sxs_: anemia sxs similar to folate deficiency → fatigue, exercise intolerance, pallor, weight loss, **glossitis**, diarrhea
* _neurologic sxs_: **symmetric paresthesias = most common initial sxs** (especially the legs)
* _lateral and posterior spinal cord demyelination and degeneration_: ataxia, weakness, **vibratory, sensory and proprioception deficits, decreased deep tendon reflexes, + babinski**
* _Dx_:
* CBC with peripheral smear:
* **increased MCV** + megaloblastic anemia (**hyper segmented neutrophils**), low reticulocytes
* **increased homocysteine levels and methylmalonic acid** → distinguishes B12 from folate deficiency
* _Tx_:
* B12 replacement
* for symptomatic anemia or neuro findings: **start with IM B12**, if adult IM = cyanocobalamin injection weekly until deficiency is corrected then once monthly)
* **pts with pernicious anemia require lifelong monthly IM therapy** (or high dose oral therapy)
* dietary deficiency = oral B12 replacement
29
G6PD Deficiency Anemia Risk Factors, Pathophys, & Exacerbating Factors
Hemolytic Anemia
* **X-linked recessive** that can cause **episodic hemolytic anemia**
* _Risk Factors_: **primarily males** (x-linked), **10-15% of African-American males**
* _Pathophys_:
* G6PD catalyzes NADP to NADPH, which protects RBCs from oxidative injury
* → loss of the NADPH causes the oxidative injury to the RBCs which leads to **denatured HGB that will then precipitate as a _Heinz Body_**
* _Exacerbating Factors_:
* **infection = most common cause**
* fava beans
* Medications: **dapsone, primaquine, methylene blue, nitrofurantoin, phenazopyridine**
30
G6PD Deficiency Anemia S/sxs, Dx, & Tx
X-linked recessive episodic Hemolytic Anemia
* _S/sxs_: **most pts are asymptomatic until times of oxidative stress**
* sxs begin 2-4 days after exposure → **back or abd -pain, sxs of anemia, jaundice**, transient splenomegaly
* neonatal jaundice
* _Dx_: **G6PD assay**
* **Heinze bodies + bite cells**
* increased LDH, increased indirect bilirubin, decreased haptoglobin
* _Tx_:
* **avoidance of trigger and supportive care**
* during acute hemolysis, tx is supportive; **transfusion is** ***rarely*** **needed**
* neonatal jaundice: phototherapy
31
Hemochromatosis
**Autosomal recessive** hemoglobinopathy caused by **excess iron absorption**
* excessive iron absorption in the intestine leads to increased **accumulation of iron** (as ferritin and hemosiderin) in **various organs → leads to organ _fibrosis_**
* _S/sxs_:
* Classic Triad: **cirrhosis, DM, & Skin Pigmentation**
* affected organs:
* **Liver (primary organ): cirrhosis** → increased risk of hepatocellular carcinoma
* **pancreas → diabetes** due to iron deposition
* **heart** → cardiomyopathy, CHF, arrhythmias
* **Joints**: arthritis of the phalangeal joints, hips and knees
* **skin**: **hyperpigmentation → “Bronze-like”**
* _Dx_: screen patient's siblings
* high levels of **serum iron, increased elevated** fasting serum **transferrin saturation and ferritin**
* decreased **total iron binding capacity (TIBC)**
* Liver biopsy to determine **degree of fibrosis**
* **_HFE gene_** testing
* _Tx_:
* **phlebotomy** → usually weekly at first then **lifelong maintenance phlebotomy Q2-4 months**
* avoid iron supplements, vitamin C or excessive alcohol consumption
* **Deferoxamine** (medication): chelation of iron → used if the patient is unable to undergo phlebotomy
32
Sickle Cell Trait
**Autosomal Recessive** → causes defective beta chain that leads to RBCS **to sickle under conditions of low oxygen**
* HbA + HbS; _HbSA = trait_
* avoid hypoxia and dehydration
* **no anemia**, resistance to malaria
* **Hematuria**
* _Dx_: **sickled cells on peripheral smear + HbS + HbA** on hgb electrophoresis
33
Sickle Cell Disease
**Autosomal Recessive Normocytic Anemia**
HbSS = disease, causes a defective beta chain
* almost exclusively in AAs, caused by homozygous inheritance of HbS → sickle-shaped RBCs clog capillaries, causing organ ischemia and infarcts
* _S/sxs_: anemia, jaundice, arthralgias, fever, **painful** (severe abd and joint pain)
* **slow healing ulcers**, N/V, cranial nerve palsies, **hepatosplenomegaly**, cholelithiasis
* _Dx_:
* **(+) HgbS on hemoglobin electrophoresis** = Definitive (no Hgb A)
* **normochromic, normocytic cells**, increased bili, and LDH
* hgb: approx 8-10, HCT 20-30%
* **reticulocytosis** (increased reticulocytes)
* **sickle cells**
* **Howell Jolly Bodies** (nuclear remnants that have not been phagocytosed due to reduced splenic function)
* _Tx_:
* **crises are tx with analgesics and other supportive measures** (oxygen, hydration)
* folic acid (penicillin prophylaxis in children)
* vaccines prolong survival
* **antisickling agents**:
* _Hydroxyurea_ may decrease the frequency of crises
* _voxeolotor_: increased oxygen affinity of HbS
* _Crizanlizumab_: prevents cell adhesion
* RBC transfusion to minimize hypoxia → Hgb \>10
* **Stem cell transplant and gene therapy = curative**
* **Median survival 60yo: infx, CVA, renal failure, pulm HTN**
34
Alpha-Thalassemia
Autosomal Recessive hemoglobinopathy
**Hypochromic microcytic anemia**
* _S/sxs_:
* **carrier**: 1 deletion = asymptomatic
* **alpha thalassemia minor**: 2 deletions = mild anemia, microcytic hypochromic
* cis deletion for *asians*
* trans deletions for *AAs*
* **alpha thalassemia major**: 3 deletions: _symptomatic_ → SPLENOMEGALY, MCHC, anemia, some need transfusion periodically
* **Hemoglobin Bart's Hydrops Fetalis**: 4 deletions = incompatible with life
* _Dx_: **decreased MCV, low hgb, _HIGH RBC_,** normal ferritin, normal TIBC and a **(+) HgB electrophoresis**
* _peripheral smear_: **target, heinz bodies** “Golf ball” looking cells and teardrop cells, microcytic
* _hgb electrophoresis_: normal hgb rations in adults with 1-2 gene deletions, detects **hgbH with 3 gene deletion**
* _Tx_: for alpha thal minor → no tx
* for alpha thal major → can do splenectomy if severe anemia or splenomegaly
35
Beta-Thalassemia
**Autosomal recessive** hemoglobinopathy
hypochromic microcytic anemia
* _Beta Thal major_: 2 of 2 beta genes damaged = significant organ damage, transfusion dependent anemia, excess alpha chains, stable as monomers, no precipitation in RBC
* _Beta Thal Minor_: 1 of 2 beta genes are damaged = mild-mod anemia
* _S/sxs_:
* thrombosis = vascular disease
* ineffective erythropoiesis → **splenomegaly, hepatomegaly, bone pain**
* hemolysis = iron deposition and gallstones → **endocrine dysfunction, cirrhosis, heart failure**
* _Dx_:
* **_very high RBC_, low MCV, _very hypochromic_**, normal ferritin, normal to low reticulocyte count, normal RDW
* _peripheral smear_: target and **teardrop cells**, basophilic stippling; nucleated RBCs → suspect thalassemia in pts with microcytosis and normal iron with increased RBC count
* _hgb electrophoresis_:
* **trait (minor)**: increased HgA2 or increased HgbF and ***decreased HgbA***
* **Major (Cooley's)**: increased HgA2 or ***increased HgbF*** (up to 90%) and little to no HgbA
* _Tx_:
* beta thal major: transfusion hgb 11-12
* folic acid daily
* **luspatercept**: RBC maturation agent
* splenectomy
* bone marrow transplant (*for severe cases*)
* iron chelation daily (need to prevent iron overload)
36
Neonatal Switch to Adult HbAA
alpha and gamma hemoglobin most prevalent just before birth, beta hgb rises just before birth
4 alpha, 2 beta in normal HgbA
37
HgbA
2alpha and 2 beta chains
normal adult Hgb
38
HgbF
2 alpha and 2 gamma chains
seen in **beta thal**
39
HgbA2
2 alpha and 2 delta chains
## Footnote
**beta thal**
40
HgbH
_4 beta chains_
## Footnote
**alpha thal**
41
Beta Chains
precipitate of just beta chains
## Footnote
**alpha thal**
42
alpha chains
precipitate of just alpha chains
## Footnote
**beta thal**
43
Acute Leukemias Overview
* onset over few weeks
* symptomatic
* immature WBCs
* decreased hgb and platelets
* need tx
* risk of death
44
Chronic Leukemias Overview
* onset over months -years
* minor sxs
* excess mature WBCs
* normal hgb and platelets
* may need tx
* chronic disease
45
Acute Lymphocytic Leukemia
* _Population_: **children**, boys\>girls, hispanics, 2-5yo
* _Pathophys_: overpopulation of immature WBCs (**lymphoblasts**) overtake normal hematopoiesis
* **_Pearl_**: *CHILD+Lymphadenopathy + bleeding + fever + bone marrow \> 20% blasts*
* _S/sxs_: **Pancytopenia →** fever & infx (leukopenia); bleeding, petechiae, purpura (thrombocytopenia); Pallor & fatigue (Anemia)
* _Dx_: **bone marrow aspiration \>20% blasts**
* **flow cytometry test**: tells you subtype of leukemia
* WBCs 5-100K, decreased hgb and platelet
* _Tx_: **combination chemo** → highly responsive with a remission \>90%
* can do stem cell transplant if relapse
46
Chronic Lymphocytic Leukemia
* _Population_: **adults**: most common form of leukemia in adults (~50yo; men \> women) **Mature B cell clonal malignancy** → lymphocyte normal range 20-40%
* _S/sxs_: often asymptomatic, fatigue, weight loss, sxs related to **pancytopenia**
* → lymphadenopathy, splenomegaly
* _Dx_: **peripheral blood smear**: Lots of B-cells, limited other leukocytes. “**smudge cells**”
* WBC \> 20K
* **Absolute lymphocyte count \> 5000 (5K)**
* _Tx_: chemo, **observation if indolent**
47
Myelodysplasia
* Pre-malignant, leukemic disorder
* _Risk factors_: **age \>65**, radiation therapy, chemo, tobacco, mercury/lead exposure
* _S/sxs_: **_often asymptomatic_**: **pancytopenia** → easy bruising, bleeding, frequent infx & fatigue
* _Dx_: bones marrow biopsy → **dysplastic bone marrow = hallmark → increased myeloblasts \<20%**
* _Tx_: goals are sx improvement and prevention of **progression to AML (blasts \>20% in bone marrow)**
* some may need intermittent blood or platelet transfusions and EPO
48
Acute Myelogenous Leukemia
* **_Pearls_**: most common presentation → **blasts** + **Auer rods** in **adult** pts **t(15:17)\*\***
* major of pts \> 50yo
* Auer rods associated with **DIC**
* _S/sxs_: anemia, bleeding, bruising, bone pain, thrombocytopenia, neutropenia
* **TUMOR LYSIS SYNDROME**
* _PE_: splenomegaly, **gingival hyperplasia**
* _Dx_: **\>20% of myeloblasts in bone marrow = GOLD STANDARD**, + myeloblasts with **auer rods**
* CBC: normocytic, normochromic anemia with normal or decreased reticulocyte count
* _Tx_: combo of **chemo + bone marrow transplant**
* tumor lysis syndrome → **allopurinol** or **rasburicase**
49
Chronic Myelogenous Leukemia
BCR-ABL translocation **t(9:22)**(**Philadelphia gene)**
* _S/sxs_: fatigue, abdominal pain, night sweats, weight loss
* → splenomegaly
* _Dx_: CBC full spectrum of WBCs, hgb and MCV = normal, platelets = slightly elevated
* **BCr-abl fusion**
* _Tx_:
* **imatinib** = tyrosine kinase inhibitor for **philadelphia +** → they inhibit philadelphia chromosome tyrosine kinase activity and myeloid leukemic cell proliferation
* **hematopoietic stem cell transplant** = most effective cure
50
Hodgkin's Disease
* _general_: most common type of **lymphoma**, _age_: **bimodal** 20s & 50s, associated with EBV infx
* _S/sxs_: **B-cell sxs are NOT common**→ fever, night sweats, weight loss, fatigue (sxs due to cytokine release from B-cells)
* **Pel-Ebstein Fever**: cyclical high fever q 1-2 weeks
* _PE_: **painless lympha**, especially of upper body lymph nodes (but may **worsen with EtOH** ingestion)
* if solitary lymph node present \> 30 days with no pain and no change → needs to be biopsied
* **contiguous spread (owls fly to the next tree)**
* _Dx_: **Reed-Sternberg cells = Pathognomonic** → B-cell proliferation with bilobed or multilobed nucleus “Owl Eyes” -→ **OWL's HOOT**
* **Excisional biopsy** of lymph node, may need bone marrow
* _Tx_: excellent 5 year cure rate (60%)
* **chemo + radiation**
* \*\*\*stage predicts outcome\*\*\*: Ann Arbor Staging: *stage I-II **single side of diaphragm***; stage III-IV both sides of diaphragm
* SEs of tx: cardiac disease if mediastinal radiation
51
Burkitt Lymphoma
high grade **non-hodgkin lymphoma**
* _Pearls_: CD20+, t(8:14), very aggressive, associated with **EBV, HIV**
* *pediatric/adolescents*.
* endemic to Africa
* _S/sxs_:
* B-cell sxs **common**,
* usually involves the **jaw and facial bones**
* * “starry sky” appearance of bone marrow biopsy
* _Tx_: **African type Burkitt lymphoma** = easily curable with chemo
* **Sporadic & HIV associated Burkitt Lymphoma** = curable with multiagent chemo
* **Rituximab** = anti-CD20 antibody
52
Follicular Lymphoma
low grade **non-hodgkin lymphoma**
* _Pearls_: small cell proliferation in *follicles*, **CD20+, t(14:18)**, usually **indolent** but hard to cure; can **progress** to diffuse large cell
* _S/sxs_: **B-sxs common**, rapid onset, SOB, intussusception, bowel obstruction and abdominal mass = more common
* → **non-contiguous, extranodal spread** → **_GI & Skin_** = most common
* _Dx_: r/o other causes of lymphadenopathy
* persistent, unexplained, enlarged lymph nodes should be biopsied
* **staging**: should be done with CT of abdomen and pelvis
* _Tx_: pts with indolent lymphoma with one or two nodes can be treated with radiation alone, **incurable\*\*\***
53
Diffuse Large B Cell Lymphoma
intermediate grade **non-hodgkin lymphoma**
* _Pearls_: CD20+, **rapidly enlarging nodes**, most common type of NHL, ave age - **70yo**
* _S/sxs_: **B-sxs common**
* SOB, intussusception, bowel obstruction, and abdominal mass = more common → **non-contiguous, extranodal spread → GI & skin** = most common
* **Painless lympha, of multiple peripheral lymph nodes**
* _Dx_: r/o other causes of lymphadenopathy
* persistent, unexplained, enlarged lymph nodes should be biopsied
* **staging**: should be done with CT of abdomen and pelvis
* _Tx_: chemo + immunotherapy (**rituxan** : anti-CD20 antibody), and stem cell transplant
54
Multiple Myeloma
* most common primary tumor of the bone/bone marrow in **pts \>50**
* all myeloma has prior MGUS stage, but only 1%/yr of MGUS pts develop myeloma
* **Malignant clonal disorder of _\*\*\*plasma cells\*\*\*_** → overproduction of **IgG** or **IgA**
* _S/sxs_: **CRAB:**
* hyper**c**alcemia
* **R**enal failure
* **A**nemia
* **B**one pain (atraumatic fractures
* _Pe_: **punched-out lytic bone lesions**
* _Dx_: serum protein electrophoresis → to determine clonality: **monoclonal immunoglobulin**
* urine protein electrophoresis → **Ig light chains (Bence Jones Protein)**
* RBC **rouleaux formation**
* _Tx_: median survival = 10 years
* complications of **infx, renal failure, spinal cord compressionb**
* **chemo +/- stem cell transplant**
* 3 med combo: **revlimid** (oral) + decadron (oral) + **bortezomib** (SQ) → disrupts protein production
55
Monoclonal Gammopathy of Undetermined Significance (MGUS)
* **pre-multiple myeloma** but NO CRAB → still has plasma cells and rouleaux formation
* **increased immunoglobulins (usually IgG)**
* _S/sxs_: asymptomatic by definition → no organ involvement
* _Dx_: Serum protein electrophoresis → **IgG monoclonal spike** (elevated but usually \<3g/dL) → usually stable over time)
* bone marrow: **\<10% plasmacytoid or plasma cells**
* _Tx_: close observation → no benefit to early tx
56
Waldenstrom Macroglobulinemia
**Lymphoplasmacytic B-cell lymphoma** that _produces excess_ **_IgM_**
* _S/sxs_: NOT myeloma → no renal, bone disease nor hypercalcemia
* **hyperviscosity** (caused by large protein: **IgM**) → bleeding, vision changes, and headache
* **nephropathy**: IgM protein acts as auto-antibody and causes immune disorder of the nerves
* “OVA”: organomegaly, viscosity, anemia
* anemia due to bone marrow failure
* _Dx_: **IgM on serum protein electrophoresis**
* bone marrow: shows plasmacytoid lymphocytes → look luke plasma cells and lymphocytes **\>10% lymphoplasmacytic infiltrate**
* _Tx_: plasmapheresis → to eliminate IgM and to **tx the severe hyperviscosity**
* immunochemotherapy → **rituximab (Rituxan)**
* Outcome: **\*\*\*\*INCURABLE\*\*\*** but course is indolent
57
Virchow's Triad
1. endothelial injury (surgery, inflammation, chemo, cancer)
2. abnormal blood flow (injured limb, sedentary, travel)
3. hypercoagulability (estrogen, cancer, hereditary)
58
Thrombocytosis
* _Primary Essential thrombocythemia_: **platelet count \>600,000** and is dx of exclusion
* _Secondary (reactive) thrombocytosis_: due to infx, inflammation, bleeding, and so on
* _S/sxs_: **splenomegaly,** pseydohyperkalemia, elevated bleeding time, **erythromelalgia** → **burning pain & erythema** of the extremities due to **microvascular occlusions**
* _Dx_: **increased platelet count**
* peripheral smear show hypogranular, **abnormally shaped platelets**
* **one marrow biopsy** → differentiate if high platelet is reactive or essential → shows an increased number of **megakaryocytes, hyperplasia, clustering**
* **_JAK2 tyrosine kinase mutation_**
* _Tx_: antiplatelet agents such as **anagrelide** and low dose **aspirin**
* **hydroxyurea**
59
Factors associated with Vitamin K activation
Factor 2, 7, 9, 10 (II, VII, IX, X)
inhibited by warfarin
VII has the shortest half life→ so it is affected first
60
unprovoked vs provoked DVT tx
_unprovoked_: anticoagulation with heparin or coumadin for 3 months
_Provoked_: should be treated **indefinitely**
61
Hemolytic Anemia Pearls
* _Autoimmune hemolytic anemia_: (+Direct Coombs test), ⇡ retic, ⇡ LDH, decreased haptoglobin, and ⇡ bilirubin (indirect)
* * _Hereditary spherocytosis_: (+) osmotic fragility test, ⇡retic, ⇡LDH, ⇣ haptoglobin, and ⇡ bilirubin (indirect) and presence of **spherocytes**
* * _G6PD Deficiency_: **after infx** or **medication** (oxidative stress) in an **african american male** (_X-linked)_ + **Heinze bodies** and **bite cells** on smear (**damaged hgb -G6PD protects RBC membrane** from oxidative damage)
62
Coarse basophilic stippling
associated with lead poisoning → microcytic anemia
63
Warfarin Skin Necrosis
associated with Protein C deficiency
64
Hepcidin
inflammatory cytokine released by the liver in pts with chronic disease
* restricts access to iron
* stops absorption of iron from the GI tract and blunts the response to EPO
65
indications for packed RBCs
* hgb \<7-8 stable patients
* hgb \<8 cardiac disease
* symptomatic anemia → dyspnea, dizziness
66
Most common transfusion rxn
fever/allergic rxn
67
Allergic Transfusion Rxn
recipient antibody (allergy) rxn to plasma proteins in transfused product
* s/sxs:
* urticaria, pruritus, and anaphylaxis
* stop transfusion temporarily
* _Tx_: antihistamines, steroids
* used washed blood products
68
Febrile Non-hemolytic Rxn
\*\*\***Most common transfusion rxn\*\*\***
platelets \> RBC
* recipient antibodies against donor WBCs release cytokines from donor white clles in stored blood product
* _S/sxs_: fever, chills, rigors
* **consider leukocyte depleted blood products**
69
Transfusion Associated Circulatory Overload (TACO)
volume overload associated with volume or speed of transfusion
* _S/sxs_: dyspnea, tachypnea, hypoxia, HTN
* _Management_: oxygen, diuresis
* cause of transfusion related deaths
* **premedicate with diuretic, transfuse slowly**
70
Transfusion Related Acute Lung Injury (TRALI)
**most common transfusion related death**
* donor anti-HLA antibodies bind recipient neutrophils that aggregate in the lung and release inflammatory cytokines
* _S/sxs_:
* hypoxia \< 6 hours after a plasma transfusion
* _tx_: supportive care
71
Delayed Hemolytic Transfusion Rxn
Pts are prior sensitized to RBC antigens with low antibody levels
* → when re-transfused with same antigen, memory antibody response results in hemolysis of transfused blood 7-14 days later
* _S/sxs_: low back pain, fever, weakness
* Self-resolves
72
Beta-Thalassemia associated with which chromosome
chromosome 11
73
Alpha-thalassemia associated with which chromosome:
chromosome 16
**A**-thala**ss**emia
ss= super sweet 16 → youre in high school so you want to get As to get into college
74
Sickle Cell Anemia associated with which chromosome:
chromosome 11
75
Which main clotting factor is not made by the liver?
Factor VIII → intrinsic
76
Wells score ≤ 2?
unlikely for a DVT → D-dimer
77
Wells score \> 2?
high risk for DVT → u/s
78
Wells Score \> 4?
Likely Pulmonary embolism
79
What do protein C and protein S do?
they inhibit clotting factors V and VIII
80
codocytes
target cells
when you go to **target** you need to scan the **codes** on your items to check out
81
echinocytes
burr cells
82
dacrocytes
teardrop cells; associated with thalassemias
83
Protein C and S provide negative feedback to which clotting factors?
V and VIII
Protein S and C: sacramento california, 9**58**18
84
Antithrombin affects which clotting factors
Anti -**T**hrombi**N**: **T**en, **N**ine, and thrombin
85
Phytonadione
generic name for vitamin K1
86
Acute Chest Syndrome
* pulmonary complication of **sickle cell anemia** :
* syndrome of **fever, respiratory distress**
* and the presence of a **new pulmonary radiodensity** on CXR
87
Luspatercept
RBC maturation agent used to treat beta-thal
88
Where are folate and B12 absorbed in the body?
* Folate: jejunum
* B12: ileum
89
if a patient receives \>10 units of packed RBCs what may happen?
the patient will continue to bleed without administration of fresh frozen plasma
* (b/c packed RBCs does not have clotting factors)
90
What Rh genotypes in a mother and father would represent a risk for hemolytic disease of the newborn?
Mother: Rh negative
Father: Rh positive
91
An African American male is placed on **hydroxychloroquine** (Plaquenil) for travel to Africa. Within six weeks he presents complaining of fatigue. CBC shows anemia. What is the diagnostic study of choice in this patient?
G6PD assay
hydroxychloroquine can cause oxidative stress
