lab

[[HGB]] [[Platelets]] [[WBC count]] [[RBC count]] [[Hematocrit]] [[MCV]] [[MCHC]] [[MPV]]

[[Hgb high]] [[Hgb normal]] [[Hgb low]]

[[RBC count high]] [[RBC count normal or low]]

Next order [[CRP]] Remember the machine can't distinguish between hemoglobin inside and outside of RBCs (i.e. can have massive [[hemolysis]] and still normal Hgb)

That's [[anemia]] (unless it's hemodilution)

Consider peripheral smear to evaluate for hypersegmental neutrophils (indicitive of megaloblastic anemia) Consider ordering [[reticulocyte count]] [[RDW increased]] [[RDW normal]] If unexpected, may be artifact of cells sticking together in machine

How's the RDW? [[Maybe a bit high]] [[It's normal]] If MCV is normal but MCHC is low, order [[iron studies]]. Iron deficiency anemia is uncommon in infants and toddlers, so a [[reticulocyte count]] is the preferred inital test for normocytic anemia in this population. There is a wide range of normal for MCV. Trends can be important--consider patient's baseline. A "normal" MCV may be a relative micro- or macrocytosis. Look for other clues including Hgbx3-HCT rule, MCHC, RDW, reticulocyte count, etc. If unexplained, request blood smear review by pathologist.

[[RDW high]] [[normal RDW]] In non-anemic patients with microcytosis, consider alpha thalassemia minor or hereditary elliptocytosis

Multiply the Hgb by 3, then subtract the hematocrit. Is the result greater than 2? [[Nope]] If yes, this suggests an [[artifactual cause]] or acute intravascular [[hemolysis]] Ordering a <i>plasma free hemoglobin</i> can help distinguish these if unsure

• Free hemoglobin (lysed red cells) in the specimen; note that the machine (and the lab tech) can’t tell whether red cells became hemolyzed in the patient, in the syringe, or in the the test tube • Something is interfering with the hemoglobin measurement (e.g. very high triglycerides) • RBCs sticking together in the machine (possibly due to a cold agglutinin) Call the lab and ask if they checked for red cells sticking together in the machine and ask them to have the pathologist look at the blood smear and call you.

[[RBC count high]] [[RBC count low]]

[[MCV low]] [[MCV normal or high]]

That's [[anemia]] (or, rarely, an artifact of cells clumping together in the machine)

[[MCV high]] [[MCV normal]] [[MCV low]] If symptomatic, order STAT type and crossmatch Compare to patient's baseline; for example a "normal" value may be low for them If rapid change in MCV (>2fL in under 48 hours) without transfusion, consider specimen mixup

What's abnormal? [[lab value]] [[condition]] [[exam finding]] [[radiology finding]] <div id="alignright">last updated 5/16/2026 - [[credits and references]]

ALT is a more specific marker of liver inflammation (AST also in muscle, kidney, brain) If asymptomatic, repeat in 4 weeks to confirm before additional workup Acute elevation: [[ALT >5000]] Chronic transaminitis: [[2-5 fold]] above upper limit of normal [[higher]] than that [[High indirect bilirubin]] [[High direct bilirubin]]

[[specific gravity]] [[pH]] [[proteinuria]]

[[Too many platelets]] [[Not enough platelets]]

Was auto differential reported? [[No auto diff]], even if WBC is within normal limits Yes, there is a [[differential]] <p style="color:red">WBC>12k or <4k plus fever, tachycardia, and/or tachypnea meets SIRS criteria</p>

[[HCT is high]] [[HCT is low]]

[[MCV high]] [[MCV normal]] [[MCV low]] • Normal range is age dependent • There is a wide range of normal for MCV, so a trend in MCV can tell you as much as an abnormal MCV • In healthy adults the MCV will change only very gradually unless there is massive hemolysis, massive pH or electrolyte shifts, transfusion, or specimen error • An abnormal MCV SHOULD NOT be ignored just because the patient is not anemic • Macrocytosis is seen in only ~25% of cases of B12 deficiency, so normal MCV does NOT rule this out

Low MCHC (hypochromic RBCs) suggests impaired hemoglobin production; evaluate for [[anemia]] and maintain high index of suspicion for iron deficiency even if MCV is normal. High MCHC can point to [[artifactual cause]]s but can also be seen in hereditary spherocytosis or megaloblastic anemia - is the [[RDW increased]]?

Look at [[RBC count]]

That's [[anemia]]

Acquired: blood doping, EPO-secreting tumors, etc. Congenital: thalessemia or other hemoglobinopathies with [[MCV low]]

Work up for [[hemolysis]] DDx: primary polycythemia (e.g. polycythemia vera); consult hematology

[[Ferritin low or low normal]] [[Ferritin not low]] [[Ferritin very high]]

Consider patient history, clinical picture before ordering EPO; rule out hemoconcentration [[EPO high]] [[EPO normal or low]]

Hemolysis (or hemolyzed specimen) Machine artifact

Most likely megaloblastic anemia due to deficiency of [[B12]] and/or folate Differential diagnosis: • marked reticulocytosis (appropriately or inappropriately increased hematopoiesis, consider ordering [[reticulocyte count]]) • myelodysplastic [[Sideroblastic anemia]] or myeloid leukemias that impair DNA synthesis • drugs that block DNA synthesis • drugs that inhibit vitamin B12 or folate utilization • congenital metabolic abnormalities (e.g. Lesch-Nyhan syndrome, methylmalonic aciduria, homocysteinuria without methylmethioninuria)

Consider aplastic anemia or bone marrow eythroid hypoplasia (sometimes due to low grade B-cell lymphomas)

This site began as my attempt to organize some of the material from the "Laboratory Medicine and Pathology 7187: Interpretation of Lab Data" course at the University of Minnesota Medical School. During residency I started incorporating some of the AFP algorithms for incidental exam and radiology findings. It is provided for educational purposes only and is not intended for medical advice or for the prevention, diagnosis, or treatment of any disease. (With apologies to <a href="https://thecurbsiders.com/">The Curbsiders</a>: "Pretty much, we aren't responsible if you screw up. You should always do your own homework and let us know if we were wrong.") As time has gone by, I've been using this site as more of a personal notebook to keep track of learning points from readings and lectures, without always documenting sources. Contact me at andrew@lymanbuttler.com with any feedback or corrections. Algorithms ("Daytonagrams") and notes for interpreting CBC and iron studies courtesy of Vanessa Dayton, MD, Department of Laboratory Medicine and Pathology, University of Minnesota Urinalysis notes courtesy Jesse C. Seegmiller, PhD, Department of Laboratory Medicine and Pathology, University of Minnesota Troponin and BNP notes courtesy Amy K. Saenger, PhD, Department of Laboratory Medicine and Pathology, University of Minnesota/Hennepin County Medical Center Coagulation notes courtesy Nicole Dodge Zantek, MD, PhD, Special Coagulation Laboratory, University of Minnesota Electrolyte and PSA notes courtesy Danni Li, PhD, Department of Laboratory Medicine and Pathology, University of Minnesota TSH algorithm from <a href="https://pubmed.ncbi.nlm.nih.gov/23760704/">Koulouri O <i>et al. Clin Med.</i> (2013) 13:282-286.</a> FE-uric acid algorithm from <a href="https://pubmed.ncbi.nlm.nih.gov/30560127/">Maesaka<i>et al. Frontiers in medicine </i> vol. 5 319. 30 Nov. 2018</a> AFP articles cited: Thyroid nodules: https://www.aafp.org/pubs/afp/issues/2020/0901/p298.html Pleural effusions: https://www.aafp.org/pubs/afp/issues/2023/1100/pleural-effusion.html Hyponatremia/hypernatremia: https://www.aafp.org/pubs/afp/issues/2023/1100/sodium-disorders-hyponatremia-hypernatremia.html Made with <a href="https://twinery.org/">Twine</a>

[[B12 low]] [[B12 normal or high]] [[Borderline or low-normal]]

Order [[iron studies]] (iron deficiency is the most common cause of anemia) Other less common possibilities include: • [[Sideroblastic anemia]] • Homozygous beta-thalassemia • Hemoglobin H disease • S-beta thalassemia • Hemoglobin SC disease

Most likely anemia of chronic disease; order [[CRP]] Other less common possibilities: hemoglobin E trait and disease; beta-thalassemia minor; two gene deletion alpha-thalassemia trait Rarely iron deficiency

C reactive protein (CRP) is produced in response to cell damage or breakdown CRP is probably more sensitive/specific than ESR (an alternative inflammatory marker) for the kind of things that will nonspecifically increase circulating ferritin

Consider ordering [[CRP]] to evaluate for inflammatory causes (anemia of chronic disease) Also consider acute blood loss or hereditary spherocytosis

Early iron deficiency presents with normal MCV, so order [[iron studies]]. Consider peripheral smear to evaluate for hypersegmental neutrophils (indicitive of megaloblastic anemia) Normal MCV can mask a combined megaloblastic and iron deficiency anemia; correlate clinically.

[[Iron saturation (TIBC) low]] [[Iron saturation not low]]

[[High LDH]] [[Low haptoglogin]] [[High indirect bilirubin]] Order peripheral blood smear if hemolysis is evident but cause is unclear Consider ordering [[reticulocyte count]] to assess bone marrow response; however, reticulocyte response may not occur for up to 72 hours after hemolysis becomes severe enough to cause anemia Kids: consider G6PD deficiency, pyruvate kinase deficiency, autoimmune causes, hemoglobinopathies, hereditary spherocytosis, hypersplenism Severe cases of B12 deficiency can mimic thrombotic microangiopathies, presenting as hemolytic anemia, thrombocytopenia, and organ damage

You need to plug in the reported % retics to this formula: ( % retics * Hct / 45 ) / 2.5 If this works out to less than 2, reticulocytes are too low (failure of erythropoiesis) If it's greater than 3, it's elevated Now go back to [[reticulocyte count]] and choose accordingly

Was this reported as a percentage or an absolute count? If it's a percentage, you have to correct it. [[How]]? [[Retics high]] [[Retics normal or low]]

If anemic, work up for occult bleeding or [[hemolysis]] Consider elevated EPO (exogenous or neoplastic), folate deficiency, polycythemia vera, drugs, heritable causes in non-anemic patients with [[MCV normal or high]] – A young reticulocyte has an MCV of 140 fl – The normal range for MCV in adults is 80-100 fl – If you are hemolyzing and have a marked reticulocytosis you can, conceivably, drive up your MCV

Check [[B12]] and folate; order [[liver labs]] and/or [[TSH]] Liver disease and hypothyroidism can lead to increased circulating unesterified cholesterol sufficient to mildly increase MCV When in doubt, get peripheral smear Differential includes: – Bone marrow erythroid hypoplasia – Ineffective production of mature red cells by bone marrow – Decreased hemoglobin production (especially early iron deficiency) – Bleeding or hemolysis combined with one of the above – Acute bleeding or hemolysis (too acute for erythropoietin response) – Alcohol abuse – Drugs – Unusual supplements (e.g. niacin megadoses) Additional considerations in peds: - Underlying kidney, liver, or thyroid disease - Parvovirus B19 - Fanconi anemia - Diamond-Blackfan anemia

The liver stores up to 7 years' supply of B12. Any inflammation (particularly liver) falsely increases the measured B12 level. Order methylmalonic acid to verify functional deficiency.

If suspicion of deficiency is high but B12 level is normal, check methylmalonic acid (B12 is a cofactor in its metabolism, so low B12 activity results in elevated MMA) Check folate Is patient taking drugs (e.g. methotrexate) that impair DNA synthesis? If unexplained, order blood smear and review results with hematopathologist; consider bone marrow biopsy The liver stores up to 7 years' supply of B12. Any inflammation (particularly liver) falsely increases the measured B12 level. Persistently elevated B12 (over 1,000 pg/mL on two measurements) in a patient not on supplements is associated with various malignancies

Check patient's Hct and click the appropriate range. 40-45: non-anemic patients don't require correction, go back to [[reticulocyte count]] [[35-39]] [[25-34]] [[15-24]] [[less than 15]]

You need to plug in the reported % retics to this formula: ( % retics * Hct / 45 ) / 1.5 If this works out to less than 2, reticulocytes are too low (failure of erythropoiesis) If it's greater than 3, it's elevated Now go back to [[reticulocyte count]] and choose accordingly

You need to plug in the reported % retics to this formula: ( % retics * Hct / 45 ) / 2 If this works out to less than 2, reticulocytes are too low (failure of erythropoiesis) If it's greater than 3, it's elevated Now go back to [[reticulocyte count]] and choose accordingly

You need to plug in the reported % retics to this formula: ( % retics * Hct / 45 ) / 3 If this works out to less than 2, reticulocytes are too low (failure of erythropoiesis) If it's greater than 3, it's elevated Now go back to [[reticulocyte count]] and choose accordingly

Iron deficiency anemia Identify underlying cause and replete iron

Mixed iron deficiency anemia & anemia of chronic disease Further studies that may be helpful: [[CRP]], hepcidin ($$$), soluble transferrin receptor ($$$)

Likely inflammatory ([[anemia of chronic disease]]); order CRP if no clear etiology

[[Iron saturation (TIBC) high]] [[Iron saturation normal]]

[[Sideroblastic anemia]]

Underlying causes to consider: acute or chronic infection, inflammation, autoimmune disorders, malignancy, renal disease, etc. More likely with elevated [[CRP]] Further studies that may be helpful: hepcidin ($$$), soluble transferrin receptor ($$$)

[[Sideroblastic anemia]] vs. [[anemia of chronic disease]] [[CRP]] helps distinguish these

The most common cause of sideroblastic anemia is a myelodysplastic syndrome. Less common causes include: • EtOH toxicity • Heavy metal poisoning (e.g. lead, arsenic) • Deficiency of pyridoxine (B6), copper, or zinc • Certain drugs (isoniazid, linezolid, chloramphenicol) Look for ringed sideroblasts on peripheral blood smear

[[TSH high]] [[TSH low]] Don't order thyroid function tests on acutely ill patients without a very good reason (likely to be abnormal due to euthyroid sick syndrome) Is patient taking biotin (B7)-containing supplements? Known to interfere with many TSH assays...

Nonspecific indicator of cellular destruction; sensitive for hemolysis

Neither sensitive nor specific for hemolysis. Inflammation can increase haptoglobin 3-4x (it's an acute phase reactant), which can mask hemolysis. Other things that can cause low haptoglobin: • advanced liver disease (it's made in the liver) • recent massive transfusion • genetic variants • megaloblastic anemias

Supports hemolysis if elevated out of proportion to direct bilirubin (increased bilirubin load presented to liver faster than conjugation can occur) Other causes: • resorption of a large hematoma • ineffective erythropoiesis • neonatal physiology hyperbilirubinemia • Gilbert syndrome • Crigler-Najjar Type 2

Platelet count >600k and/or basophils >200/μL suggests [[primary thrombocytosis]] Otherwise [[secondary thrombocytosis]]

First rule out splenomegaly or massive bleeding; consider transfusion [[I want to work it up]] - patient bruising/bleeding or otherwise symptomatic? [[I think they're fine]] - I want to rule out pseudothrombocytopenia Consider liver disease (liver produces thrombocytopoietin)

Where did the result come from? [[Desktop machine]] or other point-of-care device (e.g. i-STAT) [[Hospital lab]]

If blood was drawn into a syringe then injected into tube, please consider redrawing directly to tube to rule out clotting in the syringe. Do you have access to a hospital or reference lab in the time needed to process a new sample? [[I do]] [[No such luck]]

Order blood smear for morphology with the blood in the EDTA tube

Send purple top (CBC) tube to reference lab for CBC with auto diff and blood smear for morphology

Redraw in light blue (citrate) tube to rule out EDTA artifact Re-run on [[Desktop machine]]

Are they taking any of these? • Vancomycin • Ethanol • Chemotherapeutic agents • Thiazide diuretics • Lasix • Alpha interferon • Quinine • Sulfonamides • Aldomet • Cimetidine/Ranitidine [[Actually, yes]] [[No way]]

These suppress megakaryocyte production and could explain the patient's thrombocytopenia

Have they recently started any of (link: "these")[(goto-url: 'https://ashpublications.org/blood/article/116/12/2127/27513/Identifying-drugs-that-cause-acute')]? [[Not taking those either]] [[Yes they did]]

Heparin-induced thrombocytopenia occurs in 2-20% of patients receiving unfractionated heparin, and ~1% or less of those getting LMWH. <a href=https://www.mdcalc.com/calc/1787/4ts-score-heparin-induced-thrombocytopenia target="_blank" rel="noopener noreferrer">Click here to calculate a 4Ts score</a> If score is 3 or less, HIT is unlikely If 4 or greater, order ELISA for Heparin-PF4 Complex (or search for "heparin induced thrombocytopenia" in your EMR order set)

Patient on heparin? [[Yes they are]] [[No heparin]]

Transfusion within the last ~2 weeks? [[No recent transfusions]] [[Yes there was]]

These drugs are known to induce hapten-mediated thrombocytopenia. You would need strong suspicion for a specific drug & a need to prove it; drug dependent platelet antibody assays are expensive!

Patient is a [[neonate]] They were [[born a while ago]]

<b>Post-transfusion purpura</b> • Occurs in HPA-1a (Pl-A1) negative individuals • Usually 1-2 weeks after first blood transfusion exposure, more rapidly after any subsequent exposure • Dx: Serology for anti-platelet antibodies (ELISA) and/or HPA genotyping

<b>Neonatal purpura</b> • 1-4% of neonates have some degree of thrombocytopenia and account for 20-40% of NICU admissions • Most common cause of severe neonatal thrombocytopenia is fetomaternal platelet incompatability • Antibodies directed against human platelet antigen HPA-1a (previously known as Pl-A1) account for 90% of cases in Caucasians • Diagnosis: Maternal serology; maternal and paternal platelet antigen testing (newer approach is to genotype the parents and infant) • Treatment: prenatal IVIgG/ transfuse infant with ABO compatible/HPA-1a negative platelets

Order peripheral blood smear, discuss results with hematopathologist [[Red cell fragments]] present Smear [[doesn't have]] red cell fragments

Order [[hemolysis]] labs and coagulation testing. All of these involve hemolysis: TTP: low ADAMTS 13 activity HELLP: elevated liver enzymes HUS: test stool for E. coli and Shiga toxins DIC: elevated INR, APTT, d-dimer What if patient [[doesn't have]] hemolysis?

Rule out asplenia (functional or anatomic) If patient has [[anemia]], work it up Consider infection/inflammation (platelets are an acute phase reactant)

Order peripheral blood smear Often associated with myelid neoplasms. From most to least common: – Chronic Myeloid Leukemia (CML) – Essential Thrombocythemia – Polycythemia vera – Some cases of Chronic Myelomonocytic Leukemia – Some myelodysplastic (preleukemic) syndromes – Rare acute leukemias

MPV is useless because the platelets variably increase in size the longer they are in EDTA and no one has figured out a way to correct for this. Go back to [[CBC]]

Non-immune, non-hemolytic platelet destruction? Consult hematology; consider bone marrow biopsy Hemangiomas are another possible cause of platelet sequestration

Call the lab and request the [[differential]] as an add-on You need absolute numbers of specific leukocytes if you plan to use a WBC as the basis for an intervention (e.g. abx) Also, a normal range WBC can mask (for example) a combined neutropenia/lymphocytosis

Look at absolute counts - not percentages More than one marked cytosis/cytopenia with no obvious explanation? Order blood smear Patient is an [[adult]] Patient is [[pediatric]] [[Basophilia]]?

[[Neutrophils]] [[Lymphocytes]] [[Monocytes]] [[eosinophilia]]

[[neutrophils]] [[lymphocytes]] [[monocytes]] [[eosinophilia]]

[[neutrophils high]] [[neutrophils low]]

[[Neutrophils high]] [[Neutrophils low]]

acute bacterial infection trauma

acute viral infection sepsis medications congenital causes

[[lymphocytes high]] [[lymphocytes low]]

most commonly EBV mononucleosis Ddx: CMV, HIV, VZV, HSV, Hep A/B/C, adenovirus, pertussis

Viruses other than EBV/CMV Lymphoma Nutritional deficiencies

[[monocytes high]] [[monocytes low]]

chronic infections some acute infections (if also neutrophilic) lymphoma

aplastic anemia steroids acute lymphoblastic leukemia

allergies parasites drugs

[[Lymphocytes high]] [[Lymphocytes low]]

[[Monocytes high]] [[Monocytes low]]

Lymphoma Viruses (EBV, CMV, HIV, VZV, HSV, Hep A/B/C, adenovirus)

Viruses other than EBV/CMV Lymphoma Splenomegaly Steroids/immunosuppression

chronic infections some acute bacterial infections (with neutrophilia) alcohol withdrawal lymphoma inflammatory bowel disease sarcoidosis malignancy

Aplastic anemia Steroids Some B-cell lymphomas

Things that cause [[eosinophilia]] also tend to cause basophilia Most common causes: • hypothyroidism • renal failure Also consider: • neoplastic myeloproliferative disorders (e.g. CML) • mast cell disease • tuberculosis • inflammatory disorders (e.g. UC) • viral infections When in doubt, get blood smear

acute bacterial infections tissue damage acute blood loss or hemolysis chronic inflammation stress cigarette smoking corticosteroids lithium CML leukocyte adhesion deficiency

infections hypersplenism autoimmune disorders nutritional deficiencies neoplasms drugs

[[Free T4 high or normal]] [[Free T4 low]]

[[free T4 high]] [[free T4 normal]] [[free T4 low]] For low TSH with a thyroid nodule, order radionuclide [[thyroid uptake scan]]. Hyperfunctioning nodules are rarely malignant and do not require tissue sampling.

• TSH-secreting pituitary adenoma • resistance to thyroid hormone • non-thyroidal illness (NTI)/euthyroid sick syndrome • drugs (e.g. amiodarone) • disorders of thyroid hormone metabolism or transport • poor levothyroxine compliance • familial dysalbuminemic hyperthyroxinemia (FDH)

• autoimmune (Hashimoto) thyroiditis, hypothyroid phase • Riedel thyroiditis • s/p thyroidectomy or ablation • drugs (amiodarone, lithium, tyrosine kinase inhibitors, anti-TB) • iodine deficiency or excess • neck irradiation • thyroid infiltration (amyloid, tumor) • congenital

• non-thyroidal illness (NTI)/euthyroid sick syndrome • assay interference • isolated TSH deficiency • central hypothyroidism

• Graves' disease • toxic multinodular goiter • toxic adenoma • thyroiditis (post-viral; post-partum) • amiodarone • excessive iodine intake • exogenous thyroxine • congenital If symptomatic, assess for thyrotoxicosis using the <a href="https://www.mdcalc.com/calc/3816/burch-wartofsky-point-scale-bwps-thyrotoxicosis">Burch-Wartofsky Point Scale</a>

• subclinical hyperthyroidism • recent treatment for hyperthyroidism • drugs (steroids, dopamine) • non-thyroidal illness (NTI)/euthyroid sick syndrome • assay interference

[[high specific gravity]] [[low specific gravity]] [[fixed/unchanging]] across multiple UAs Specific gravity can be used to estimate [[urine osmolarity]]. Multiply the last two digits by 30 (for example, if SG=1.012 then 12x30=360 osm)

Isothenuric: severe kidney damage, cannot concentrate or dilute.

• diabetes insipidus: very low SG, 1.001-1.003 • renal tubular damage (glomerulonephritis, pyelonephritis)

• excess water loss: diarrhea, sweating, fever, vomiting • adrenal insufficiency • hepatic disease • CHF

[[low pH]] [[high pH]]

• high protein diet • medications: ammonium chloride, mandelic acid • acidosis • uncontrolled diabetes

• postprandial (counteracting gastric acid secretion) • vegetables, dairy • medications: sodium bicarbonate, potassium citrate, acetazolamide • urinary tract infection • bacterial contamination

• acetaminophen • hepatic ischemia • unusual causes of viral hepatitis (e.g. HSV)

Common causes: • alcohol • metabolic associated steatotic liver disease (calculate <a href="https://www.mdcalc.com/calc/2200/fibrosis-4-fib-4-index-liver-fibrosis">FIB-4 score</a>) - FIB-4 [[less than 1.3]] - FIB-4 [[1.3 or more]] Current guidelines* recommend calculating FIB-4 on ALL patients with T2DM, incidental imaging findings consistent with fibrosis, or overweight/obese with at least one additional risk factor (eg. HTN, HLD) Also consider extrahepatic causes: celiac disease, hyperthyroid, rhabdomyolysis Uncommon: • hepatitis B • hepatitis C • hemochromatosis • drug-induced liver injury (most often acetaminophen, Augmentin, nitrofurantoin, statins, sulfonamides, allopurinol) Rare: • autoimmune hepatitis • alpha-1 antitrypsin deficiency • Wilson disease • primary biliary cholangitis <div id="alignright"> *Kanwal, F., Bril, F., Wai-Sun Wong, V., Adams, L. A., Pfotenhauer, K., Skolnik, N., Wright, E. E., Jr, Eckel, R. H., Noureddin, M., Loomba, R., Allen, A. M., Bansal, M. B., Godwin, K. M., El-Serag, H. B., & Shubrook, J. H. (2026). Clinical Care Pathway for the Risk Stratification and Management of Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease. Gastroenterology, S0016-5085(26)00198-8. Advance online publication. https://doi.org/10.1053/j.gastro.2026.01.047

usually obstructive; clinical picture is abdominal pain, fever, palpable gall bladder consider RUQ U/S Also consider Dubin-Johnson and Rotor syndrome

Consider • autoimmune hepatitis • hemochromatosis • toxic hepatitis

High-sensitivity troponin T? Click here: [[HSTT]] Single elevated measurement may reflect [[non-MI etiology]]. Elevation is sensitive, but not specific, for type 1 MI; low positive predictive value esp. in the absence of other criteria Beware overdiagnosis of type 2/NSTEMI which often leads to extensive additional workup with no patient-oriented benefit (AFP Dec 2024) Guidelines are vague about the absolute frequency of testing; baseline, 3, and 6 hour samples may be sufficient depending on the assay and cutoffs used [[baseline cTn ≤ 0.20 ng/mL]] [[baseline cTn > 0.20 ng/mL]] (assumes reference range is <99%ile = <0.01 ng/mL)

myocardial infarction (per <a href="https://www.ahajournals.org/doi/10.1161/CIR.0000000000000617">universal definition</a>) if at least one of these also present: • Ischemic symptoms • ECG changes indicative of new ischemia • Pathologic Q waves • Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality • Intracoronary thrombus identified by angiography or autopsy

• recent intense exercise • recent cardiac procedures • tachyarrhythmia/bradyarrhythmia • heart failure • renal failure • pulmonary embolism • acute myocarditis • demand from systemic illness (e.g., sepsis) • false elevation due to heterophile antibodies (e.g. SLE, RA, hemolysis, immune complex formation)

change of 0.03 ng/mL or greater is considered a clinically [[significant change]] if change is lesser in magnitude, consider [[non-MI etiology]]

change of 20% or greater is considered a clinically [[significant change]] if change is lesser in magnitude, consider [[non-MI etiology]]

This does NOT apply to nt-pro-BNP! Will update soon... [[BMI > 35]] [[BMI < 35]] (adipocytes metabolize BNP)

If less than 55 pg/mL, HF unlikely Greater than 55: obtain echocardiogram

[[GFR < 60]] (renal failure) [[GFR > 60]]

If less than 200 pg/mL, HF unlikely Greater than 200: obtain echocardiogram

If less than 100 pg/mL, HF unlikely 100-500: consider echocardiogram Greater than 500: HF likely, confirm with echocardiogram

[[PT/INR prolonged]] [[PT/INR normal]]

[[aPTT high]] [[aPTT normal]]

[[aPTT prolonged]] [[aPTT is normal]]

[[TT high]] [[TT normal]]

[[TT prolonged]] [[TT Normal]]

[[Thrombin time high]] [[Thrombin time normal]]

[[thrombin time prolonged]] [[thrombin time normal]]

• unfractionated heparin • lupus anticoagulant

• Factor VIII, IX, XI or XII deficiency/inhibitor • von Willebrand disease (if Factor VIII deficient) • HMWK and Prekallikrein deficiency • Lupus anticoagulant

• Mild hypo/hyper fibrinogenemia • A little unfractionated heparin or direct thrombin inhibitor • D-dimer/fibrin(ogen) degradation product elevation • Lupus anticoagulant

• Normal coagulation function • Factor XIII deficiency/inhibitor • Von Willebrand disease (with normal Factor VIII) • Platelet disorder • Connective tissue problem • Mild coagulation factor deficiency • Lupus anticoagulant

• Disseminated intravascular coagulation (DIC) • Liver disease • Low fibrinogen, multifactor deficiency • Direct thrombin inhibitor, lots of heparin, bridging • Lupus anticoagulant

• Factor II, V or X deficiency/inhibitor • Multiple clotting factor deficiencies • Warfarin • Direct Xa inhibitors • Vitamin K deficiency • Lupus anticoagulant

• Lupus anticoagulant

• Factor VII deficiency/inhibitor • Mild factor II, V, or X deficiency/inhibitor • Warfarin • Vitamin K deficiency • Lupus anticoagulant

Before ordering, consider: • Is this screen (link: "appropriate")[(goto-url: 'https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/prostate-cancer-screening')] for this patient? • DRE in the past week? (can artificially elevate) • Is UTI or prostatitis likely? • Prostate biopsy in the past 6 weeks? (5-50x increase) • Recent bike riding? • Ejaculation in past 24-48 hours? • Being treated for BPH? (e.g. ~50% PSA reduction on finasteride) [[under 2 ng/mL]] [[2-4 ng/mL]] [[4-10 ng/mL]] [[>10 ng/mL]] <div id="alignright"> Brawer, M. K. CA <i>Cancer J Clin 1999</i>, 49, (5), 264-81

1% probability of prostate cancer

15% probability of prostate cancer

If this is the first elevated PSA, consider repeating in a few months to rule out transient causes or lab error If repeat PSA still elevated, may consider ordering percent free PSA for further risk stratification: <img src="https://lymanbuttler.com/media/images/fpsa.png"> Can also consider IsoPSA if available (better specificity)

very concerning for prostate cancer, >50% likelihood

[[Na]] [[K]] [[Mg]] [[Ca]] [[phosphate]] [[HCO₃⁻]]

[[Mg high]] [[Mg low]]

• chronic renal failure • iatrogenic • hyperparathyroidism • adrenal insufficiency • hemolysis

– Drugs: cyclosporine, cisplatin, diuretics, aminoglycoside antibiotics – Dietary deficiency – Alcoholism – GI loss – Cellular hypoxia – Eclampsia of pregnancy – Loss through skin (burns) – Parathyroid hormone deficiency (sepsis or hypoparathyroidism) – Diabetes – Collection in tubes with anticoagulants citrate, oxalate, or EDTA can falsely lower Mg

Corrected for albumin? (Ca⁺⁺ and H⁺ compete for binding sites on albumin) [[Of course I remembered to do that]] <a href="https://www.mdcalc.com/calc/31/calcium-correction-hypoalbuminemia">How do I do that</a> Could also order ionized Ca if in doubt To work up calcium derangements, consider evaluating: • PTH (first ask if patient is taking biotin supplements - notorious source of interference) • Serum and urine phosphate • Serum magnesium • Renal function • 25-OH Vitamin D • 1,25-(OH)2 Vitamin D (if renal involvement suspected) • Alkaline phosphatase

[[Phosphate high]] [[Phosphate low]]

[[hyponatremia]] less than 135 [[hypernatremia]]

[[hypokalemia]] [[hyperkalemia]]

Choose your favorite hyponatremia decision tree. I prefer <a href="https://clinicalproblemsolving.com/wp-content/uploads/2017/05/Updated-Hyponatremia-Schema-Feb-2020.pdf">The Clinical Problem Solvers</a> because it avoids subjective volume status assessment. If Na < 125 with neurologic symptoms, initiate treatment with [[hypertonic saline]] before workup If etiology is not obvious from history and exam, order serum osmolarity; if serum osm less than 275 (hypoosmolar hyponatremia) order [[urine osmolarity]] and urine Na (unless patient is on loop diuretics, in which case, determine [[FE-uric acid]]). Serum osm [[275-295]] Serum osm [[over 295]] Serum osmolality can be estimated using <a href="https://www.mdcalc.com/calc/91/serum-osmolality-osmolarity">this calculator</a>, but beware of possible causes of <a href="https://emcrit.org/pulmcrit/osmolal-gap/">osmolal gap</a>

• inadequate free water intake relative to losses (most common); calculate patient's (link: "free water deficit")[(goto-url: 'https://www.mdcalc.com/calc/113/free-water-deficit-hypernatremia')] • deficient hypothalamic thirst mechanism (e.g. supresellar/infrasellar tumors, trauma, vascular disease) • diabetes insipidus • Cushing syndrome • hyperaldosteronism • iatrogenic (salt tablets, sodium bicarbonate, lithium, etc.) Reference: Braun MM, Barstow CH, Pyzocha NJ. Diagnosis and management of sodium disorders: hyponatremia and hypernatremia. Am Fam Physician. 2015 Mar 1;91(5):299-307. PMID: 25822386.

[[pseudohyperkalemia]] If new EKG changes attributable to this, push 1g IV calcium gluconate, repeat EKG in 5 minutes, may repeat dose up to twice [[GFR < 15]] [[GFR > 15]]

• Hemolysis • Delayed separation (leak from red blood cells) • EDTA contamination (confirm with serum calcium conc.) • Fist pumping/relaxing during draw • Thrombocytosis(plateletsreleasepotassium during clotting) • Lymphocytosis (release of potassium due to white blood cell consumption of glucose)

[[HBsAg positive]] [[HBsAg negative]] Source: <a href="https://www.cdc.gov/hepatitis/hbv/pdfs/serologicchartv8.pdf">CDC</a>

[[IgM anti-HBc positive]] [[IgM anti-HBc negative]]

[[anti-HBs positive]] [[anti-HBs negative]]

[[Anti HBc positive]] [[Anti HBc negative]]

[[anti HBc positive]] [[anti HBc negative]]

Interpretation unclear; 4 possibilities: 1) resolved infection (most common) 2) false positive anti-HbC (thus susceptible) 3) low-level chronic infection 4) resolving acute infection (window period)

susceptible to infection; vaccination recommended

immune due to past infection

immune due to vaccination

acute Hepatitis B infection

chronic Hepatitis B infection

<div id="alignright"> [[start over]]

– Acute and/or chronic renal failure – Metabolic acidosis (certain types cause transcellular shift of phosphate) – Cellular destruction (trauma, rhabdomyolysis, burns, massive hemolysis, leukemia, etc.) – Hypoparathyroidism – Excessive intake of phosphate-containing meds/foods (i.e. milk-alkali syndrome: antacids, laxatives, enemas, vitamin D, milk)

– Transcellular shifts (e.g., glucose and insulin cause phosphate to move into cells) – GI loss (nausea, vomiting, diarrhea) – Renal loss (renal reabsorption defects, diuretic use, alcohol, hyperparathyroidism, hypomagnesemia, vitamin D deficiency)

Patient could have multiple etiologies that drive Na in opposite directions; consider ordering [[urine osmolarity]] Rare causes: • pseudohyponatremia (lab artifact) • extreme hypertriglyceridemia (depends on assay; contact lab) • hyperproteinemia/paraproteinemia (e.g. multiple myeloma)

Hyperosmolar hyponatremia; some other solute is present in such high concentration that it draws free water into the vasculature, diluting Na: • hyperglycemia (<a href="https://www.mdcalc.com/sodium-correction-for-hyperglycemia">correction calculator here</a>) • IV contrast • mannitol Renal failure or heavy EtOH use may be present, but do not explain hyponatremia on their own

[[less than 100]] [[over 100]] Urine osmolarity can be estimated using [[specific gravity]]. Multiply the last two digits by 30 (for example, if SG=1.012 then 12x30=360 osm)

• primary psychogenic polydipsia • poor solute intake (e.g. heavy EtOH use, beer potomania, "tea and toast" diet)

urine Na [[over 40]] urine Na [[20-40]] urine Na less than 20 suggests [[low effective arterial blood volume]] as RAAS activation stimulates renal Na retention Diuretics affect Na excretion, so don't order FENa on these patients; order [[FE-uric acid]] instead

challenge with small volume of NS If serum Na increases, this suggests [[low effective arterial blood volume]] If serum Na stays the same or decreases, it's likely SIADH (as ADH should be suppressed by fluid bolus)

With clinical signs of volume overload: heart failure, cirrhosis, nephrotic syndrome Otherwise hypovolemia (vomiting, diarrhea, SBO, burns, diuretics, primary adrenal insufficiency, salt-wasting nephropathy); replete with NS

• adrenal insufficiency • hypothyroidism • thiazide diuretics • SIADH (supported by serum uric acid < 4) • cerebral salt wasting

If etiology unclear, consider ordering urine protein-creatinine ratio and albumin-creatinine ratio. Albumin and total protein are generally elevated to a similar degree in glomerular disease. Total protein elevated out of proportion to albumin could suggest multiple myeloma, etc. Also see here: https://www.aafp.org/pubs/afp/issues/2000/0915/p1333.html#afp20000915p1333-t4

KDIGO definition of AKI: Increase of ≥1.5x over baseline over 7 days, or, ≥0.3 mg/dL absolute increase over 48 hours

urine uric acid x serum Cr -------------------------- x 100% serum uric acid x urine Cr FE-uric acid greater than 12% is is 86% sensitive and 100% specific for SIADH. 4% - 11% is consistent with primary polydipsia or reset osmostat Less than 4% suggests decreased effective arterial blood volume (dehydration, edematous states)

[[CBC]] [[electrolytes]] [[acid-base]]/ABG/VBG [[creatinine]] [[liver labs]] [[urinalysis]] [[TSH]] [[BNP]] elevated [[troponin]] elevated [[coagulation studies]] [[PSA]] [[hepatitis B serology]] [[iron studies]] [[B12]] [[C. difficile]]

[[thyroid nodule]]

[[Hyperfunctioning]] ("hot") nodule [[Nonfunctioning]] ("cold") nodule

[[thyroid nodule]] [[pleural effusion]]

order TSH and ultrasound [[TSH low]] [[TSH normal or high]]

Options include: • Medical management with methimazole or PTU; propranolol for symptoms • Radioiodine ablation • Thyroidectomy

[[small, bilateral]] large or unilateral effusions [[require further evaluation]] Consider POCUS

Small bilateral pleural effusions in patients with decompensated heart failure, cirrhosis, or kidney failure are likely transudative and do not require diagnostic thoracentesis If condition worsens, effusion may [[require further evaluation]]

Further evaluate with ultrasound, CT, or lateral decubitus plain film [[minimal size or <1cm]] [[larger than this]] and/or [[complex features]]

Treat underlying conditions If condition worsens, effusion may [[require further evaluation]]

[[complex features]] on US or CT (e.g. hyperechoic, loculations, septations, nodules) [[no complex features]]

Consult pulmonology or thoracic surgery Complicated parapneumonic effusion or empyema may require chest tube drainage, tPA, dornase, or thorascopy

U/S guided thoracentesis Labs: Gram stain, cell count with diff, culture, cytology, protein, LDH, pH, serum protein, serum LDH, others as indicated (e.g. TB) [[exudative]] [[transudative]]

For simple parapneumonic effusions, treat underlying pneumonia Effusions with [[complex features]] or those that fail to improve may require consult Also consider PE or heart failure (Light's criteria is ~100% sensitive for exudates, but is less specific; 20% of HF patients on diuretics will have fluid ratios consistent with exudate)

Treat underlying condition (e.g. heart failure, liver disease, kidney disease)

• Lifestyle management • Avoid alcohol • If high risk (T2DM and/or 2+ metabolic risk factors) consider MASH-directed therapy (e.g. Wegovy, resmetirom) and repeat FIB-4 in 1 year • If not high risk: FIB-4 every 1-2 years

If more than 2.67, fibrosis is very likely - refer to GI If 1.3 - 2.66: • Elastography, e.g. Fibroscan (if BMI > 36.65, MRI is preferred) • CMP, CBC, A1c, lipid panel • Can consider Enhanced Liver Fibrosis (ELF) score but this relies on some fairly exotic labs

• 3% NaCl at 1-2mL/kg/hr • Recheck sodium hourly • Once corrected, check q6h for 24 hours • Do not correct Na faster than 8 mEq/L over 24 hours in chronic hyponatremia

HSTT results are more likely to be elevated than earlier-generation troponin assays; consider [[non-MI etiology]] HSTT < 6ng/L after 6 hours of symptoms rules out myocardial injury HSTT between [[6-99ng/L]]? HSTT > 99ng/L rules in myocardial injury

Repeat HSTT in 2 hours An increase of 7 ng/L or greater is a [[significant change]] Otherwise, consider another repeat in [[2 more hours]], admission for observation, discharge with close follow-up, or stress testing

An increase of 20% above baseline is considered a [[significant change]]

[[Hypercalcemia]] [[Hypocalcemia]]

If symptomatic or Ca > 14, intiate treatment BEFORE completing workup If PTH is significantly elevated it's probably primary hyperparathyroidism [[PTH normal]] or mildly elevated [[PTH low]] or low normal

Is patient taking bisphosphonates, cinacalcet, chelators (e.g. citrate, lactate, EDTA), phenytoin, or foscarnet? (Including blood products, which contain citrate) [[Low Mg]] [[Low PTH and/or high phosphate]] [[Low vitamin D]] [[High PTH]] (or clinical signs of extravascular calcium deposition)

• Milk-alkali syndrome • Thiazides • Lithium • Thyrotoxicosis • Adrenal insufficiency • Pheochromocytoma • Rhabdomyolysis • Primary hyperparathyroidism Consider 24 hr urine calcium to check for familial hypocalciuric hypercalcemia (FHH)

Check PTHrp - if elevated, malignancy likely [[PTHrp normal]]

[[1,25-dihydroxycholecalciferol elevated]] [[1,25-dihydroxycholecalciferol low or normal]]

• sarcoidosis • tuberculosis • granulomatosis with polyangiitis • histoplasmosis • Crohn's disease • Berylliosis • Lymphoma

Check 25-hydroxycholecalciferol; consider vitamin D toxicity if elevated If not elevated, obtain SPEP, UPEP, serum free light chains to assess for multiple myeloma If these are unrevealing, consider vitamin A toxicity, hyperthyroidism

Hypomagnesemia can reduce PTH secretion or cause PTH resistance Replenish Mg and recheck Ca

Hypoparathyroidism; consider: • genetic • post-surgical • autoimmune • post-radiation • infiltrative • HIV

replenish and recheck Ca

• kidney disease • tumor lysis • pancreatitis • acute respiratory alkalosis • osteoblastic mets • sepsis/acute illness • pseudohypoparathyroidism

[[pulmonary embolism]] [[hepatitis C]] without cirrhosis

[[normotensive]] [[hypotensive]] (SBP < 90, or decrease of at least 40 for 15 minutes]] <div id="alignright">Morillo, R., Moores, L., & Jiménez, D. (2017, July). Prognostic scores for acute pulmonary embolism. Seminars in Thrombosis and Hemostasis (Vol. 43, No. 05, pp. 486-492).

Patient over 80, tachycardic to 110+, BP below 100, SpO2 below 90%, or history of cancer and/or chronic cardiopulmonary disease? [[No - lower risk]] [[Yes - elevated risk]] (any of these increase risk of death to at least 8.9%)

High risk; acute mortality 15%-70% Admit to ICU Unfractionated heparin drip Systemic thrombolysis (e.g. tPA) ?catheter-directed thrombolysis; consider IR consult

Calculate <a href="https://www.mdcalc.com/calc/4004/bova-score-pulmonary-embolism-complications">Bova score</a> If 4 or less, [[PE risk is intermediate-low]] If 5 or greater, [[PE risk is intermediate-high]]

Hestia criteria: do ANY of the following apply to the patient? • hemodynamically unstable • medical or social indication for hospital admission > 24 hours • thrombolysis or embolectomy needed • active bleeding or high risk of bleeding • need supplemental O2 for > 24 hours to maintain SpO2 > 90% • PE diagnosed while on anticoagulation • IV pain medication > 24 hours • creatinine clearance < 30 mL/min • severe liver impairment (clinician judgment) • pregnant • documented history of HIT No - pass Hestia criteria, very low risk; consider discharge on DOAC Yes - [[PE risk is intermediate-low]]

Risk of death, shock, or recurrent VTE 4%-18% Admit to inpatient Initiate LMWH 1mg/kg BID, transition to DOAC

Risk of death, shock, or recurrent VTE 27%-42% Admit to inpatient Initiate LMWH 1mg/kg BID, transition to DOAC Consider ICU Consider IR consult

Consider MUDPILES: M — Methanol U — Uremia (chronic kidney failure) D — Diabetic ketoacidosis P — Paracetamol (acetaminophen), Propylene glycol I — Infection, Iron, Isoniazid, Inborn errors of metabolism L — Lactic acidosis E — Ethylene glycol, Ethanol S — Salicylates

https://emcrit.org/ibcc/nagma/ Will flesh this out more eventually

bicarb elevated is [[alkalemia]] bicarb decreased is [[acidemia]]

[[MCV high]] on CBC? (Things that cause megaloblastic anemia also affect platelets) [[It wasn't]]

[[acidemia]] (pH < 7.38) [[alkalemia]] (pH > 7.42) <p style="font-size:60%;">Reference: https://www.aafp.org/pubs/afp/issues/2025/0200/acid-base-interpretation.html NB: //-osis// and //-emia// are frequently confused. An -osis is a process and an -emia is something in the blood. So, an acidosis is a process that tends to lead to acidemia. A patient with a well compensated acidosis may not be acidemic.</p>

[[PaCO₂ elevated]] [[PaCO₂ decreased]]

[[PaCO₂ is elevated]] [[PaCO₂ is decreased]]

Respiratory acidosis Use this formula to determine if there is appropriate metabolic compensation: • Acute: HCO₃⁻ = 24 + • Chronic: Consider mixed process if significant deviation from expected compensation

Metabolic acidosis [[anion gap]] [[non-anion gap]] Use Winter's Formula to determine whether there is appropriate respiratory compensation: Expected PaCO₂ = (1.5 x serum HCO₃⁻)+(8±2) Consider mixed process if significant deviation from expected compensation

Metabolic alkalosis Use this formula to determine if there is appropriate respiratory compensation: PaCO₂ = 0.7 x (HCO₃⁻ - 24) + 40 Consider mixed process if significant deviation from expected compensation

Respiratory alkalosis Use this formula to determine if there is appropriate metabolic compensation: • Acute: • Chronic:

Colonization is common. Is history suspicious (health care exposure, recent antibiotics, etc)? Is patient clinically ill? (abdominal pain, 3+ liquid stools per 24 hours) [[C. diff PCR positive]]

Follow up with C. diff glutamate dehydrogenase antigen test and enzyme immunoassay toxin test; these may be done by reflex depending on your order sets + antigen / + toxin = active infection* - antigen / - toxin = colonization* + antigen / - toxin = colonization* Results are suggestive, interpret in clinical context

Correct deficiency, identify & address underlying cause. Oral B12 is noninferior to IM, even in severe deficiency, Roux-en-Y, and atrophic gastritis Common causes include metformin, PPIs, H2 blockers, vegan diet, problems with ileum (Crohn's, resection, celiac, bariatric surgery) If no obvious cause, consider autoimmune gastritis, H. pylori, pernicious anemia. Workup includes anti-intrinsic factor (specific), anti-parietal cell (sensitive), EGD with biopsies

Does patient have any of the following: prior hepatitis C treatment, cirrhosis, HBsAg positive, current pregnancy, known or suspected HCC, prior liver transplant? If yes - refer to GI If no - appropriate for [[management in primary care]]

Obtain CBC, CMP, INR, HIV, Hep A ab, HBsAg, HCV quant PCR HCV genotype not required for treatment, but may be required by insurance Calculate FIB-4 score to evaluate for fibrosis/cirrhosis - FIB-4 [[less than 1.3]] - FIB-4 [[1.3 or more]] - no need to delay initiation of treatment unless clinically decompensated cirrhosis FIB-4 > 3.25 is presumptive for cirrhosis - refer to GI (or if clinically apparent) Treatment options: • glecaprevir 300mg/pibrentasvir 120mg (Mavyret) 8 weeks - preferred in MN (send to specialty pharmacy) • sofosbuvir 400mg/velpataasvir 100mg (Epclusa) 12 weeks Both are generally well tolerated. Check for drug interactions before starting. Consider follow-up at 4 weeks to assess adherence/response (LFTs, HCV PCR) Test of cure (normal LFTs, undetectable HCV PCR) 12 weeks after completion