Hematology for Family Pracfce When to Treat and When to Refer

Hematology for Family Pracce When to treat and when to refer

Karen deGenevieve MSN, FNP,BC OCN How long do cells live?

• Red blood cells live approximately 120 days.

• Platelets live 8 -11 days.

• White blood cells live about 4 days.

There are millions of RBCs in just one drop of blood. People who live at higher altudes have more (like in the mountains of Peru). They are produced in the bone marrow of large bones at a rate of 2 million per second. In the minute it took you to read this, you made 120 million of them!

First thing to do with an abnormal CBC is to repeat it and get a smear to pathology, manual diﬀ, and reculocyte count.

MICROCYTOSIS:

Low MCV (mean corpuscular volume) under 80. Low MCH (mean corpuscular hemoglobin) under 27. Low MCHC (mean corpuscular hemoglobin concentraon) under 30.

MACROCYTOSIS: High MCV over 93 High MCH over 33 High MCHC over 37

NORMOCYTIC ANEMIA: NOMAL INDICIES

DEFINITIONS

Reculocyte: The youngest of the circulang red cells, normally they comprise about 1% of the red cell populaon. They are increased in response to bleeding, or hemolysis, or in response to treatment with B 12, iron, of folic acid. Decreased in the presence of a suppressed or otherwise abnormal bone marrow, aplasc anemia, pure red cell aplasia or following chemotherapy.

Nucleated red blood cells: Are NORMOBLASTS. Are not normally seen in peripheral blood. They usually indicate the presence of severe degrees of hemolysis, profound stress, hypoxemia, or myeloﬁbrosis.

Erythrocyte: A mature red blood cell that contains hemoglobin, conﬁned within a lipid membrane, it’s main purpose is to transport oxygen.

Leukocyte: Is a white blood cell. 5 types of leukocytes are classiﬁed by the presence or absence of granules in the cytoplasm of the cell. The agranulocytes are lymphocytes and monocytes. The granulocytes are neutrophils, basophils, and eosinophil's.

Leukocytes funcon as phagocytes of bacteria, fungi, and viruses, detoxiﬁers of toxic proteins that may result from allergic reacons and cellular injury, and immune system cells.

Platelet: The smallest cells in the body, they are formed in the bone marrow and some are stored in the spleen, they do not contain hemoglobin and are essenal for the coagulaon of blood and in maintenance of hemostasis.

Anemia Testing Click here for topics associated with this algorithm

INDICATIONS FOR TESTING Fatigue, weakness, pallor, dizziness, fainting

ORDER CBC with Platelet Count and Automated Differential (including RBC indices and morphology on manual differential) Reticulocytes, Percent & Number

Anemia present on CBC (males Hgb <13g/dL, females Hgb <12g/dL) AND Corrected reticulocyte index ≥2.5

No Yes

Classify by RBC indices Fragmented cells on peripheral smear

Normocytic, normochromic Microcytic, hypochromic Macrocytic Yes No (normal MCV, MCHC) (low MCV, MCHC) (high MCV) (suggests hemolysis) (suggests hypoproliferation) (suggests maturation defects) (suggests maturation defects)

Suggests Metabolic defect (see PNH B12 deficiency, (less Bone marrow disorder acute blood Consult topic) (infiltration, aplasia) commonly folate deficiency) – see loss (eg, Hemoglobinopathies (eg, Inflammation Iron deficiency hemmorhage) sickle cell) – see Hemolytic Autoimmune disease Megaloblastic Anemia Chronic disease Testing Algorithm Anemias Testing Algorithm Chronic renal disease Thalassemia – see Autoimmune destruction Critical illness Drug effect Hemoglobinopathies topic Excessive alcohol use Splenic sequestration Chronic endocrine Sideroblastic anemia RBC membrane defect – see disorders Hypothyroidism Lead toxicity Myelodysplasia – see Hemolytic Anemias Consult Aplastic anemia, pure topic red cell aplasia Myelodysplastic Syndromes Consult topic Intravascular hemolysis – see Hemolytic Anemias Consult topic Abnormal peripheral smear

ORDER No Iron and Iron Binding No Yes Capacity Ferritin Vitamin B12 & Folate High TIBC Low/normal TIBC Workup based on Low iron Normal/high ferritin smear Low ferritin Low/normal iron characteristics Abbreviations and Formula Bone marrow Iron deficiency Suggests MCV = mean cell volume biopsy may be anemia Inflammation MCHC = mean cell hemoglobin concentration Chronic disease necessary TIBC = total iron binding capacity Thalassemia Reticulocyte correction for anemia:

If no obvious chronic disease present, Hgb 1 _ consider bone marrow biopsy; for ReticCount% x Htc x Maturation time correction Thalassemia suspicion, consider (use 2% for most patients) hemoglobin electrophoresis

Auer Rods: observed in Blasts associated with AML Red Cell Morphology and associated Condions

Auer Rods: Anisocytosis: observed in Blasts associated with AML Various types of anemia Acanthocytosis (spur cells): Alcoholic cirrhosis, post splenectomy, hemolyc anemia Anisocytosis: Various types of anemia Basophilic Sppling: Fine: various anemias Course: lead toxicity and thalassemias Bite Cells: Chemical poisoning, G-6PD deﬁciency, hemolyc anemia Burr Cells: Myeloproliferave states, heparin therapy, uremia, Chronic renal disease, bleeding, pepc ulcers Howell-Jolly bodies: Post Splenectomy, megaloblasc and hemolyc anemias

Hypersegmented neutrophils: megaloblasc anemias, pernicious, B12, and folate deficiencies Dohle bodies: (toxic granulaon are usually seen together) Acute infecon, pneumonia, scarlet fever, measles, Dohle bodies: (toxic granulaon are usually seen together) Acute infecon, pneumonia, scarlet fever, measles, sepcemia, pregnancy, burns Reacve lymphocytes: (Downey cells) mono, CMV, viral hepas, chronic inflammatory disease Smudge Cells: atypical lymphocytosis, CML Schistocytosis: cardiac valve disease, DIC, severe burns, uremia Spherocytes: (helmet cells) hereditary spherocytosis, thermal injuries, immune and hemolyc diseases, TTP, DIC Rouleaux: mulple myeloma, elevated protein Target cells: chronic liver disease, iron deficiency, post splenectomy Tear drop cells: Thalassemias, pernicious anemia, Myeloproliferave disorders.

Band Neutrophils: normal 5-11% increased # = LEFT SHIFT (stress, infecon, Myeloproliferave disease) Basophils: <2% are normal. Allergic reacon, hypothyroid, chronic hemolyc anemia, post splenectomy Eosinophils: increased in asthma, hay fever, extensive skin lesions, Metamyelocyte: Myelocyc hyperplasia Myelocyte: CML, AML Metamyelocyte: Myelocyc hyperplasia Myelocyte: CML, AML Plasma cells: Not usually seen in peripheral blood. Chronic infecons, autoimmune disorders, alcoholic liver disease. Monocytes: increased in chronic neutropenia, IBD, chronic infecon, CMV, TB an can be elevated in AMML.

Evaluang Anemia

Number one reason for microcyc anemia is bleeding, either GU or GI. Ask the right quesons. A good physical exam and a good history is essenal to your invesgaon. Don’t forget family history.

Megaloblastic Anemia Testing

Click here for topics associated with this algorithm

INDICATIONS FOR TESTING Patient presents with megaloblastic anemia and/or neurologic symptoms

ORDER Vitamin B12 Folate (for patient with known risk factors)

Low or normal folate Vitamin B12 >400 pg/mL Vitamin B12 100-400 pg/mL Vitamin B Low folate levels only 12 levels and high suspicion <100 pg/mL for deficiency

ORDER Folate deficiency Low Occasionally, clinician may Methylmalonic Acid, Serum ORDER find normal levels of B12 in or Plasma (Vitamin B 12 Folate, RBC symptomatic patients (usually Status) No neurologic symptoms) B deficiency 12 folate deficiency Normal MMA and homocysteine may be appropriate to confirm B 12 <0.4 µmol/L >0.4 µmol/L deficiency, as homocysteine may have a role in detecting folate or B12 deficiency Not pernicious anemia

ORDER Optional antibody testing when MMA >0.4 µmol/L Methylmalonic Acid, Serum or (MMA >0.4 µmol/L confirms B12 deficiency ) Plasma (Vitamin B12 Status) Homocysteine, Total ORDER Intrinsic Factor Blocking Antibody

Both elevated Positive Negative

Pernicious ORDER Confirmed B12 anemia Gastric Parietal Cell deficiency Antibody, IgG

Positive Negative

Pernicious ORDER anemia Gastrin

<100 pg/mL >100 pg/mL

Not pernicious Pernicious anemia anemia (indirect confirmation)

Iron preparaons:

Ferrous gluconate orally is less likely to cause GI upset and is more tolerated than ferrous sulfate. It is equally absorbable with less side eﬀects. Comes in may strengths and is generally OTC. Severe iron deﬁciency may require 325 mg TID. Most paents don’t take it as directed for a variety of reasons. Nausea and conspaon are the biggest reasons.

I never order ferrous sulfate, for those reasons.

There are many condions that can interfere with oral iron absorpon and or cause iron deﬁciency:

Being older, poor tolerance of oral iron preparaons Inﬂammatory bowel disease, ulcerave colis Gastric surgery and gastric bypass H. Pylori, autoimmune gastris and celiac disease. Chronic kidney disease and dialysis Cancer paents

IV iron preparaons: (use them when paents cannot tolerate oral)

AVOID IM: It’s painful, stains the buocks, and has variable absorpon. Case reports have also described development of sarcomas.

Iron Dextran (Infed): Black Box warnings for anaphylaxis, requires pre medicaons and takes long to give. Usually including premeds and test dose, 4-6 hours. Dosing is by weight and Hgb. (Chart) can be up to 1.5 Gms. More than a Gram doesn’t work any beer.

Ferumoxytol (Feraheme): Given in 2 doses, one week apart. 510 mg Oen given with premeds and has an increase in second dose reacons.

Iron sucrose (Venofer): Should have a test dose. Given in mulple doses, not over 300 mg. Used in CKD, and in the seng of dialysis.

Ferric carboxymaltose (Injectafer): is a colloidal iron hydroxide complex with a ghter binding of elemental iron. It’s a 15 minute infusion and doesn’t require premeds and is given in NSS 750 mg in 2 doses, one week apart.

Monitoring:

For chronic iron deﬁciency anemia paents that require ongoing IV iron treatments, monthly CBC’s and iron studies including ferrin. Treat again when ferrin goes below 50.

Oral iron treatment F/U should be checked monthly during replacement unl repleted. Connue oral iron up to 3-6 months aer normalizaon of iron levels to replete iron stores. When ferrin is normalized, a trial oﬀ iron for 3 months and recheck CBC, iron, TIBC and ferrin.

If the cause of the iron deﬁciency has been treated, no further iron should be necessary. (normalizaon of periods, post uterine oblaon, GI bleed is successfully treated, etc.) Hemolytic Anemias Testing Click here for topics associated with this algorithm

ORDER Presence of the following may provide clues to the etiology of the anemia CBC with Platelet Count and Increased reticulocyte count INDICATIONS FOR TESTING Automated Differential Abnormal peripheral smear Patient with anemia and Reticulocytes Polychromasia, spherocytes, schistocytes, sickle cells, evidence of hemolysis Lactate Dehydrogenase stomatocytes, Heinz bodies, basophilic stippling, unusual red cell Haptoglobin inclusions, and agglutination Bilirubin Note: lack of any of the above does not rule out hemolytic anemia

Consider DIC Proceed based on above findings TTP DIC Increased HELLP Consider Sickle cell disease – High-performance liquid Sickle cells ORDER HUS Microangiopathic Schistocytes, diverse genotypes: SS, SC, chromatography (HPLC) Normal D-Dimer Mechanical RBC destruction thrombocytopenia SE, Sβ thalassemia, S Lepore Clinical presentation cardiac valve Vasculitis consistent with TMA Congenital 5' Malignant Consider 5' No nucleotidase hypertension nucleotidase testing deficiency Basophilic Acquired Pregnant stippling ORDER ADAMTS13 Activity Consider OR Consider serum Consider Yes lead E. coli Shiga-like Toxin by EIA lead level testing HELLP If infection suspected, poisoning (dependent on presentation) consider Unusual red Polychromasia malaria, bartonella cell inclusions only with or ORDER (oroya fever), babesia Consider ADAMTS13 Positive without platelet PNH PNH, High Sensitivity, RBC and WBC testing Normal activity <10% Shiga toxin decrease

Consider one or more Atypical Consider of the following tests TTP HUS Polychromasia without HUS Pyruvate kinase Pyruvate kinase other reproducible deficiency Hexokinase morphologic abnormality Hexokinase deficiency Glucose phosphate ORDER Other enzyme defects RBC Band 3 isomerase Consider Protein Consider molecular No Reduction in ORDER RBC membrane testing disorder Warm Hereditary Osmotic Spherocytes, ORDER (hereditary Consider No autoimmune Spherocytosis Fragility, pyropoikilocytes, Direct Acquired spherocytosis, cold Positive for hemolytic anemia Erythrocyte elliptocytes or Agglutination Coombs hereditary agglutinins complement Direct Coombs (usually acanthocytes (Anti-Human elliptocytosis, disease (Anti-Human Yes positive) Globulin) autoimmune Globulin) hemolysis) Cold Cold Yes agglutinins agglutinins testing disease

IgG+ +C3 Consider Consider one or more of Glucose-6-Phosphate the following tests Isopropanol heat No Yes dehydrogenase For hemoglobin stability testing Cold agglutinins disease, paroxysmal deficiency disorders, Heinz Glucose-6- cold hemoglobinuria (PCH) Unstable hemoglobin consider bodies Phosphate defects HPLC, genetic Recluse spider Autoimmune hemolytic anemia Dehydrogenase Glutathione testing venom, clostridium (consider drug induced, metabolism defects (G6PD) 2 Mutations sepsis hemolytic disease of the Confirm PCH with Donath Hemoglobin H Enzymes of newborn, autoimmune disease) Landsteiner testing disease glutathione cycle

Tests: CBC, with manual diﬀ, reculocyte count, LDH, Haptoglobin, Bilirubin.

Findings: Elevated reculocyte count Elevate LDH Decreased Haptoglobin < 25 (if LDH and Haptoglobin are normal, 90% probability it’s not hemolyc anemia) Posive Direct Coombs test Increased indirect Bilirubin

Peripheral smear: Fragmented RBC (schistocytes or helmet cells Spherocytes seen in hereditary scherocytosis Spur cells seen in liver disease Tear drop RBC’s with circulang nucleated RBC indicang the presence of marrow involvement. Treatment for Hemolyc Anemia (Autoimmune):

Diagnosis – Accurate diagnosis of warm agglunin autoimmune hemolyc anemia Treatment for Hemolyc Anemia (Autoimmune):

Diagnosis(AIHA) requires documentaon of the presence of red cell destrucon (hemolysis) – Accurate diagnosis of warm agglunin autoimmune hemolyc anemia along with demonstraon of the presence of an autoanbody or complement on the surface of the paent's red cells.

paents with underlying cardiac disease, AIHA can present as a medical emergency, requiring immediate packed red cell transfusion. conﬁrmed, we recommend immediate instuon of treatment with glucocorcoids conﬁrmed, we recommend immediate instuon of treatment with glucocorcoids over splenectomy,

Poorly responsive, severe, or resistant disease

For adults, it is preferred splenectomy over Rituximab, as it is the only modality with potenal for long-term cure, while rituximab is the treatment of choice for adults who either are not surgical candidates or refuse surgery.

Third-line treatment – For those who have failed treatment with both splenectomy and rituximab, should instute immunosuppressive or cytotoxic agents such as azathioprine (Imuran), cyclophosphamide, or cyclosporine.

Obviously you have already referred to Hematology!

CAUSES OF REACTIVE THROMBOCYTOSIS

NON MALIGNANT HEMATOLOGIC CONDITIONS:

ACUTE BLOOD LOSS ACUTE HEMOLYTIC ANEMIA ACUTE IRON DEFICIENCY ANEMIA TREATMENT OF VITAMIN B DEFICIENCY REBOUND EFFECT AFTER TREATMENT OF IMMUNE THROMBOCYTOPENIA REBOUND EFFECT AFTER ETHANOL-INDUCED THROMBOCYTOPENIA

MALIGNANT CONDITIONS:

METASTATIC CANCER LYMPHOMA REBOUND EFFECT FOLLOWING USE OF MYELOSUOORESSIVE AGENTS

ACUTE AND CHRONIC INFLAMMATORY CONDITIONS:

RHEUMATOLOGIC CONDITIONS, VASCULITIS, IBS, CELIAC DISEASE

TISSUE DAMAGE:

THERMAL BURNS MYOCARDIAL INFARCTION SEVERE TRAUMA ACUTE PANCREATITIS POST-SURGICAL PERIOD, ESPECIALLY POST-SPENECTOMY CORONARY ARTERY BYPASS PROCEDURES

INFECTIONS:

CHRONIC INFECTIONS AND TUBERCULOSIS

EXERCISE

ALLERGIC REACTIONS

FUNCTIONAL AND SURGICAL ASPLENIA

REACTION TO MEDICATIONS:

VINCRISTINE EPINEPHERINE, GLUCOCORTICOIDS INTERLEUKIN-1B ALL-TRANS RETINOIC ACID THROMBOPOIETIN, THROMBOPOITIN MIMETICS LOW MOLECULAR WEIGHT HEPARINS (ENOXAPARIN)

Hydroxyurea:

Used mostly these days for Essenal Thrombocythemia. It can be used in CML. Dosing is 500 mg tablets trated to keep the platelet count below 400K. Monitoring CBC’s should be weekly at ﬁrst and then changed to every 2 weeks unl stabilizaon occurs. It can drop Hgb and WBC’s so traon can be tricky. Usually changes in dosing shouldn’t be sooner than every 2 weeks as it takes that long to stabilize on a new dose.

It is an anneoplasc agent and is carcinogenic. Advise sun protecon and monitor for malignancies.

Adjustments for lower Creanine clearance. Most people tolerate it without side eﬀects. Causes macrocytosis Eltrombopag (Promacta):

Colony smulang Factor; Hematopoiec Agent; Thrombopoiec Agent. Used for Chronic immune idiopathic Thrombocytopenia (ITP) Max dose is 150 mg daily. Titrate to maintain platelets with lowest dose. Weekly CBC monitoring unl Platelets get up to 30K and you are seeing an upward trend, the CBC’s every 2 weeks. Pricing: 12.5 mg tabs # 30 = $4124.09 75 mg tabs # 30 = $11,509.09 Monitor liver funcons Should be taken on an empty stomach Can be used in Hepas C for thrombocytopenia with cauon. Dosing is usually tolerated well. SE: fague, nausea, diarrhea, elevated LFT’s are the most common.

Anagrelide (Agrylin):

Anplatelet Agent, used for Essenal Thrombocythemia (ET) Well tolerated, and can be used with Hydroxyurea on tough cases. Cauon in Hepac impairment. Inial dosing is 0.5 mg 1 to 4 mes daily Max daily dose of 10 mg Titrate up slowly, must not be increase by more than 0.5 mg a day in any one week. Most paents will stabilize between 1.5 and 3 mg daily. Generic form available

Pricing: 0.5 mg (100) = $585.70 (generic) 1 mg (100) =$1171.35 (generic) Monitoring parameters CBC Q 2 days during the ﬁrst week with pretreatment EKG and CMP frequently during treatment. Monitor for intersal lung disease. SE: palpitaons, chest pain, CHF, fague, edema, rash, diarrhea, nausea, elevated LFT’s

Hematopoiec Growth Factors:

Erythropoien, Granulocyte and granulocyte-macrophage colony smulang factors (G-CSF and GM-CSF), Thrombopoien

The family of glycoproteins known as the hematopoiec growth factors (HGFs) plays a major role in the proliferaon, differenaon, and survival of primive hematopoiec stem and progenitor cells, as well as in funconal acvaon of some mature cells. These effects are mediated by high affinity binding of the HGFs to specific receptors expressed on the surface of the target cells. Recombinant HGFs are administered in the following clinical sengs:

Transient bone marrow failure following chemotherapy Hematopoiec stem cell and progenitor cell mobilizaon Recovery from hematopoiec cell transplantaon Myelodysplasc syndrome Aplasc anemia Some forms of neutropenia Inherited bone marrow failure syndromes Human immunodeﬁciency virus (HIV) infecon-associated neutropenia Chronic anemias (eg, renal failure, prematurity, chronic disease/inﬂammaon, HIV infecon) Reducing the need for perioperave blood transfusion

Potenal toxicies of the recombinant HGFs include the following (see 'Toxicity of colony-smulang factors' above and 'Toxicity of erythropoien' above):

Transient leukopenia

Systemic reacons (eg, ﬂu-like symptoms, capillary leak, hypertension, thrombosis)

Producon of deleterious neutralizing anbodies

Possible smulaon of malignancy

Possible enhancement of HIV replicaon

Mulorgan failure when used in sickle cell syndromes PEARLS: 1. ANC (absolute neutrophil count) is the neutrophil # on the differenal of a CBC. Always order CBC with diff so you can find this number. If it is < 1.5 or below 1500 you have neutropenia. 2. Thrombocytopenia alone, may be due to platelet clumping. Have the lab do a manual diff to verify if there is clumping. If so have the next CBC, have drawn in a sodium citrate tube. Clumping can be seen with EDTA tube. Monocytosis:

A number of condions which cause neutrophilia can also cause monocytosis, making this combinaon a relavely nonspecific finding. These include pregnancy, the asplenic state, inflammatory (eg, sarcoidosis, inflammatory bowel disease) and autoimmune condions, depression, and treatment with corcosteroids or colony smulang factors. Monocytosis may also accompany condions associated with neutropenia, presumably as a compensatory mechanism.

A large number of infecons have been associated with monocytosis including brucellosis, varicella-zoster, bacterial endocardis, tuberculosis, malaria, typhoid fever, syphilis, and trypanosomiasis.

Monocytosis may also be seen in certain malignancies, such as Hodgkin lymphoma. Neutrophilia with monocytosis may also suggest chronic myelomonocyc leukemia, one of the myelodysplasc disorders. Addional associated ﬁndings in this condion are anemia, thrombocytopenia and abnormal cellular maturaon (eg, macrocyc red cells, defecve lobulaon in neutrophils, and abnormal size and granulaon in platelets). Hemochromatosis Testing Click here for topics associated with this algorithm

INDICATIONS FOR TESTING Suspicion of hemochromatosis (family history, compatible symptoms)

ORDER Iron and Iron Binding Capacity Note: Test includes serum transferrin saturation (STS) AND Ferritin (SF)

STS <45% and STS ≥45% and/or normal SF elevated SF

No further Repeat STS and SF testing at tests this point

STS ≥45% Repeat STS and SF: elevated for age and sex SF tests at 2- (esp. if >2x normal) year intervals

Secondary If both elevated, iron do liver biopsy overload

No Yes

FOR ADULTS, ORDER FOR PEDIATRICS, Treat Hemochromatosis (HFE) 3 CONSIDER underlying Mutations HJV (HFE2) gene sequencing cause (accounts for >90% of mutations in (accounts for >90% of cases) Caucasians)

H63D/H63D C282Y/H63D C282Y/wt C282Y/C282Y Negative H63D/S65C C282Y/S65C Positive

Hemochromatosis CONSIDER Monitor STS Hemochromatosis confirmed confirmed HAMP (HEPC) gene Consider liver biopsy sequencing Consider alternative gene (accounts for <10% of cases) testing (TFr2, FPN) ORDER Ferritin AND Aspartate Aminotransferase, Serum or Plasma

Ferritin ≥1000 μg/L Ferritin <1000 μg/L Aspartate aminotransferase (AST) abnormal Aspartate aminotransferase (AST) normal

Liver biopsy with hepatic iron concentration Phlebotomy Monitor STS

Family screening

INDICATIONS FOR TESTING Bone pain, recurrent infections, anemia, lytic lesions on plain film

Perform baseline screening Rule out CBC with Platelet Count and Automated Differential Chronic infections such as HIV Metabolic profile, which should include Immunoglobulin deficiencies such as Calcium, Serum or Plasma AND Common Variable Immunodeficiency (CVID) BUN/Creatinine, Serum or Plasma Chronic inflammatory processes such as Protein, Total, Serum or Plasm systemic lupus erythematous, liver disease Albumin, Serum or Plasma by Spectrophotometry Other malignancies Lactate Dehydrogenase, Serum or Plasma If negative for other diseases

ORDER Protein Electrophoresis with Reflex to Immunofixation Electrophoresis Monoclonal Protein Detection, Quantitation and Characterization, IgA, IgG, and IgM, Serum 24 hr urine protein electrophoresis AND Monoclonal Protein Detection Quantitation & Characterization, SPEP, IFE, IgA, IgG, IgM, Serum (Protein electrophoresis with reflex testing may occasionally miss IgA MGUS or multiple myeloma [MM]) Immunofixation Electrophoresis, Qualitative, Gel

Serum M protein ≥3 g/dL

No Yes

Abnormal baseline testing or suspicion for multiple myeloma (MM) ORDER Bone marrow biopsy Skeletal survey

No Yes

ORDER Serum free light chain ratio (Kappa/Lambda Quantitative Free Light Chains with Ratio, Serum) to diagnose oligosecretory myeloma and non-secretory myeloma ≥10% plasma cells* <10% plasma cells Bone lesions present No bone lesions present Monoclonal Abnormal baseline Normal baseline testing gammopathy of testing Normal Abnormal undetermined FLC ratio FLC ratio significance (MGUS) ORDER Asymptomatic MM Bone marrow biopsy (smoldering) Repeat Skeletal survey MM evaluation in 3-6 months Bone lessions

Repeat No Yes evaluation in 3 months

MM <10% plasma cells ≥10% plasma cells

Likely Asymptomatic MGUS (smoldering) MM *This criterion is unnecessary if bone lesions are present

Repeat evaluation in Repeat evaluation in 3-6 months 3 months

UP TO DATE has apps for cell phone, expensive but great!

ARUP Consult apps for cell phone, great reference for algorithms. iHematology apps for cell phone, quick reference to describe smear morphology.

Medical Lab Tests for cell phones labtestsonline.org

WHEN TO REFER

1. PANCYTOPENIA 2. PLATELETS TREND DOWN OVER TIME AND ARE STAYING UNDER 100 K 3. YOU CAN’T FIND A REASON FOR IRON DEFICIENCY 4. UNEXPLAINED LEUKOCYTOSIS 5. UNEXPLAINED ADENOPATHY…. GET IT BIOPSIED! 6. INTOLERANCE TO ORAL IRON AND PERSISTANCE OF IRON DEFICIENCY WITH NEGATIVE WORKUP 7. YOU HAVE A BAD FEELING AND TOO MAY ABNORMALS ON THE SMEAR...

MY ADVICE: GET TO KNOW YOUR LOCAL HEMATOLOGIST AND ASK FOR ADVICE. THEY MAY HAVE A FRIENDLY NP TO TALK TO. SHE OR HE MAY HAVE GOOD ADVICE!!!