University:
Michigan State University
Course:
MED 609 | Hematology Clerkship
Academic year:

2021
Views:

46

Pages:

40
Author:

Dixie Summers

Gives lymphoid common progenitor and myeloid common progenitor gives the following stem cells Kidney EPO Erythropoietin Maturation O2 Sensor Blood vessel Reticulocytes ✓ Erythropoiesis is inﬂuenced by EPO which is a hormone secreted by the kidneys ✓ EPO secretion is stimulated by hypoxia Reticulocytes are slightly immature red blood cells , that have reminants of RNA material , they become mature within 1-2 days in peripheral circulation Mature RBCs > No nucleus Definition: Anemia is operationally defined as a reduction in one or more of the major RBC measurements: Hemoglobin concentration, g\dL > the volume Hematocrit, Hct percentage of red RBC count (vol%) blood cells millions\L most commonly used index (RBC) in blood These are all concentration measures res WHO's deﬁnition of anemia The cut-off value defining anemia has been determined by convention as the value at -2 SD from the mean or the 2.5th percentile of the normal distribution of a healthy iron-replete population. WHO's Hemoglobin thresholds used to define anemia in adults (g/dl) Women, non-pregnant (>15yrs) 12. Women, pregnant 11. pregnant ladies have increased plasma volume (lower Hg concentration) Men (>15yrs) 13. ✓ There's nothing such called "anemia of elderly people" >> Hg is NOT affected by age so it's not acceptable to have an anemic old aged person and saying that this is the result of his age ✓ BUT erythropoiesis may SLIGHTLY decrease in some old men as a result of the decrease in testesterone (but not below all the previous numbers) Severity of Anemia/g/dl/WHO Classification Non‐pregnant women (15 yrs and above) Mild Moderate Severe here most of patients have symptoms 11‐11.9 8‐10.9 <8 Pregnant women 10‐10.9 7‐9.9 <7 Men (15 yrs and above) 11‐12.9 8‐10.9 <8 Anemia • Understanding anemia Anemia is either a – Disease ‐ to be treated on its own merits – Condition ‐ a secondary manifestation of another disease Or a liver disease \ Malaria \ DIC • Causes Blood loss OR imbalance btw synthesis & destruction (1&3) (pathogenesis) – Decreased production – Blood loss – Hemolysis 90-120 days PATHOLOGY, SYMPTOMS, AND SIGNS OF ANEMIA increased destruction Anemia + Jaundice >> Hemolysis Hematinics deﬁciency Bone marrow failure Anemia of increased destruction or blood loss can be compensated to certain level this doesn't occur in anemia caused by reduced production Symptoms at rest (as resting Tachycardia) >> sever anemia or the body fails to compensate knowing the level of activity at which patient start having symptoms is important in assessing the severity The symptoms evaluate the severity of the anemia and the ability of the patient's body to compensate Clinical Evaluation of Anemia: History • Proper History; including history of bleeding and systemic illness • Dietary History • Past History • Family History • Drug history • Travel History ✓ Haematinic (Iron , folate , vitB12) deﬁciency ✓ Vegetarian periodic hemolysis >> as in G6PD deﬁciency hemoglobinopathies \\ RBCs disorders Antifolate chemotheraputics \\ Certain drugs can cause Hemolysis Malaria The “Anemia Syndrome” due to tissue hypoxia 1‐ Dizziness 2‐ Fatigue 3‐ Shortness of breath especially on exertion 4‐ Headaches 5‐ Chest pain/ palpitations 6‐? Heart Failure Clinical evaluation of anemia: Physical Examination • • • • • Pallor > skin , mucosal membranes Resting Tachycardia Helpful in assessing the severity Postural Hypotension Look for signs of anemia Look for signs suggestive of type Examine for splenomegaly/Hepatomegaly Look for signs suggestive of cause Examine for signs of systemic disease in acute blood loss Later As in anemia of chronic disease ( such as CT diseases ) Factors that influence symptomatology and severity of symptoms btw patients gives the body time to compensate >> better tolerated anemia Acute or chronic Cardiovascular status Additional symptoms related to cause Additional symptoms related to type of anemia • Any intravascular hemolysis • • • • CVS is needed for compensation by increasing the CO > Higher HR & SV Remember : Intravascular hemolysis occurs when erythrocytes are destroyed in the blood vessel itself, whereas extravascular hemolysis occurs in the hepatic and splenic macrophages within the reticuloendothelial system. Laboratory Evaluation of Anemia usually it's ~= 3.3*HB Low HB >> Low Hct • Complete blood count including HB, RBC, MCV, RDW WBC , diff WBC ✓ A red cell distribution width (RDW) ✓ If high >> your RBCs aren't not equal in size (anisocytosis) • Reticulocyte count **** A reticulocyte : ✓ Normally present in peripheral circulation but not more than 1-2% of total RBC count in the peripheral circulation ✓ Converted to mature RBCs within 1-2 days ✓ has remnant RNA that can be stained by Methylene Blue ✓ Doesn't have nucleus but has rRNA (ribosomes) so still it's capable of producing Hemoglobin (remember globin is a protein produced by ribosomes) ✓ Increased in Anemia of blood loss & anemia of increased destruction • Peripheral smear • Other specialized tests >> Blood ﬁlm > to see the shape and the size of the RBCs or certain signs suggestive to certain diseases According to your suspicion Reticulocytes won't be distinguished from mature RBCs using the conventional stain so we use a supravital stain called "Methylene Blue" that stains the rRNA particles Notice that they are larger than mature RBCs Anemia Classification: Two main approaches 1‐ Biologic or kinetic approach –Determined by reticulocyte count 2‐ Morphology. mean corpuscular volume –Determined by MCV High or Normal Normocytic , Microcytic , Macrocytic Acute vs. chronic –Signs and symptoms Morphological Classification of Anemia A‐ Normocytic/normochromic (normal MCV &MCH): acute blood loss, Hemolysis, ACD, BM failure B‐ Microcytic/hypochromic (MCV<78, MCH <26): IDA, Thalassemia C‐ Macrocytic (MCV>98): megaloblastic or Non-Megaloblastic anemias.MDS. Mean corpuscular hemoglobin ✓ The reticulocyte count must be corrected " if the patient is Anemic" according to his Hct and HB ✓ No need for correction if the patient is normal number not % ✓ Correction is either : corrected RC or Absolute RC ✓ Normal Absolute RC is (60,000 -100,000) ✓ From the corrected RC we calculate the Reticulocyte production index Reticulocyte production index >(2.5 is the cutoff) More than 2.5 > Hemolysis or hemorrhage Less than 2.5 > Anemia of decreased production The calculation is necessary because the reticulocyte count is misleading in anemic patients. The problem arises because the reticulocyte count is not really a count but rather a percentage (it reports the number of reticulocytes as a percentage of the number of red blood cells). In anemia, the patient's RBCs are depleted, creating an erroneously elevated reticulocyte count. The reticulocyte count In other words : More than 2.5 > proper response > the bone marrow is compensating for anemia less than 2.5 > under response ( the problem in the production itself) • Corrected retic. = Patients retic.(3%) x (Patients Hct(30)/45) : 3(%)x30/45 = 2% • Retics index (RPI) = corrected retic. • Retics index (RPI) = corrected count/Maturation time reticulocyte count/Maturation time (Maturation time = 1 for Hct=45%, 1.5 for 35%, 2 for 25%, and 2.5 for 15%.) example above: 2/1.75= 1.14 • Absolute reticulocyte count = retics % x RBC number. 6 Example: 1.1% x 4.96 x10 = 55,000/μl 6 12.2% x 2.05 x10 = 250,000/μl Patient Hct Normal Hct To correct for shift reticulocytes. Shift reticulocytes : less and less mature reticulocytes that need more time in the circulation to become mature , They are present in sever anemia More than 100,000 >> The bone marrow is compensating Less than 60,000 >> the problem is in the production itself Anemia of Increased destruction or blood loss Anemia of low production pyruvate kinase or G6PD deﬁciencies memranopathies : spherocytosis , electrocytosis if it's associated with iron or folate def thalassemia and sickle cell anemia anemia of chronic inﬂammation Or Mechanical Destruction as in prosthetic heart valves ** Combined etiologies of anemia : ✓ Blood loss > if chronic may cause IDA (combined) ✓ Thalassemia > Hemolysis later may be combined with iron or folate def Low H b=Anem ia MCV Low= m icrocytic N orm al=norm ocytic H igh=m acrocytic Ferritin M easure B 12 + folate Fe deficient Fe norm al Establish cause Anem ia of chronic disease or hem oglobinopathy N orm al O bvious cause Low Establish cause C ause not obvious C onsider bone m arrow R eticulocyte count H em olysis or blood loss high low Anem ia of chronic disease R enal failure M arrow failure Iron Deﬁciency Anemia (IDA) Remember : Normal MCV is between 80 and 100 fL. Microcytic Hypochromic Anemia: Diagnosis Low MCV • Mild (MCV > 70 fl) – Iron deficiency – Thalassemia – Lead toxicity – Sideroblastic anemia – Anemia of chronic disease Most common other DDx for Microcytic hypochromic anemia • Severe (MCV < 70 fl) – Iron deficiency – Thalassemia Evolution of Iron Deficiency Anemia • Depletion of body Iron stores only but No anemia 2 Steps • Iron Deficiency with anemia • Ferritin: The Best Marker for Iron Deficiency in “adults” ✓ Low ferritin and low HB is diagnostic for IDA ✓ Remember : ferritin is an "acute-phase reactant" that becomes elevated in response to inﬂammation , So the patient may have Crohn's disease that caused IDA but ferritin still high due to the inﬂammation ✓ Iron content in the body : 3-4 g \\ most of it used by RBCs in HB synthesis ✓ Normal loss everyday is very little ~1-2 mg , should be easily met by Normal diet ✓ There's no method for Iron excretion from the body ✓ Iron def >> decrease intake \ increase loss \ increase demand pregnancy blood loss Nutritional or malabsorption Major Categories of the cause of IDA 1‐ Nutritional: poor or absent red meat consumption 2‐ Blood loss: GI/GU/: benign or malignant lesions. Hemosiderinuria 3‐ Malabsorption: Gluten enteropathy 4‐ Repeated pregnancies most common in females after menopause and in men most common cause in females in their reproductive age Heme iron (ferrous +2) found in red meet is more easily absorbed than non-heme iron (ferric +3) found in vegetables which needs high acidity to get reduced to ferrous in order to be absorbed celiac Disease , diseases affecting stomach acidity , bariatric surgery >> increased demand ** IDA isn't a ﬁnal Dx u have to establish the cause and try to treat it Symptoms & Signs of IDA : >> symptoms of Anemia syndrome due to hypoxia >> Frontal blading , Koilonychia , Angular chelittis , glossitis , Pica , Restless leg syndrom ✓ IDA + Dysphagia + Esophageal web >> Plummer-Vinson syndrome (PVS) ✓ Association : Celiac disease , Crohn's , Achlorhydria , Colon cancer , PUD , heavy menstruation ..etc ** Regarding the labs : ✓ Low HB ✓ Low MCV ✓ Low MCH ✓ High RDW ✓ Low Reticulocytes ✓ Low serum Fe test measures the blood's ability to attach itself to iron and transport it around the body. ✓ Low ferritin High as the body try to compensate for low Fe by increasing tranferrin and increasing Transferrin receptor ✓ High Total iron-binding capacity (TIBC) ✓ High Soluble Transferrin receptor (STFR) ✓ Low % Transferrin saturation with iron low as there's low Fe and high tranferrin ✓ Normal WBCs (except if there's inﬂammation) ✓ High or normal platelets (high due to EPO similarity to TPO & also as an acute phase reactant) ** Note : Most accurate test that gives the diagnosis of IDA deﬁnitely : Bone marrow biopsy , but it's painful and invasive so we depend on labs ** TIBC & STFR can be used to see if the iron stores are depleted when the patient has ongoing inﬂammation or whatever makes ferritin elevated as an acute phase reactant ✓ Iron Deﬁciency blood ﬁlm :& Anisocytosis,abnormal SevereAnemia Hypochromia Poikylocytosis: shaped red blood cells Microcytosis + Severe Hypochromia + Anisocytosis + Poikylocytosis Iron Deficiency Anemia having RBCs that are unequal in size. = increased RDW Pencil shaped Elliptocyte Notice the increased central pallor >>> Hypochromia Biconcave shaped RBCs with central pallor that doesn't exceed 1\3 of the total volume of the cell Target cells can be seen in IDA but must be associated with Anisocytosis Hypochromia with target cells but without Anisocytosis: Thalassemia Trait suggest the Dx of TRANSPORT PROTEINS/Fe DMT1 (Divalent Metal Transporter 1) (Tranports from lumen into the enterocytes) FERROPORTIN1 (Transports from enterocytes to circulation) What is HEPICIDIN?? HEPICIDIN is the key regulator of iron in our body. Is a peptide hormone. Its molecular weight is 25 Kda. Highly folded structure. Present in inactive form;prohepcidin(60aa) and its active form is hepicidin(25aa). produced by the liver • Hepcidin lowers iron absorption in the intestine ,lowers iron releasing from hepatocytes and macrophages High Hepcidin = Serum iron is decreased. Mechanism of action of hepicidin The major mechanism of hepicidin is THE REGULATION OF TRANSMEMBRANE IRON TRANSPORT. It binds to FERROPORTIN ,forms hepicidin‐ ferroportin complex ,which is degraded in the lysosomes and iron is locked inside the cells(mainly enterocytes,hepatocytes and macrophages). Hepicidin Regulation So when hepicidin levels are low ,iron exporting cells have abundant ferroportin and thus releases iron into plasma.When hepicidin concentration increases it binds to ferroportin and thus iron is retained in the cells. Affecting levels of Hepcidin Hepicidin/Ferroportin Hypoxia/Anemia leads to decrease in hepcidin Inflammation leads to increase in hepcidin Ferroportin ✓ Anemia or hypoxia >> low Oxygen >> Low Hepcidin >> high Uptake of diet iron & high Iron only release from hepatocytes andexporter macrophages >> iron serum levels The cellular iron inhighvertebrates. ✓ inﬂammation >>in high Interleukin‐6 >> High Hepcidin >> Low iron serum levels Present enterocytes,macrophages,placenta >> anemia of chronic disease or inﬂammation and the hepatocytes. Disease States Hepcidin deficiency, physiological = Haemochromatosis Hepcidin excess – anaemia of chronic disease Red > anemia in general blue > IDA Case one Symptoms of “Anemia Syndrome” due to tissue hypoxia Hints indicating IDA 24 yr old female complains of Dizziness, Fatigue, Shortness of breath especially on exertion and Headaches for the last 4 months. She has been losing scalp hair. She does not eat red meat and has reported heavy menstrual bleeding. Her physical exam is shown Lab and Xray test are shown Likely Diagnosis ✓ Normal MCV >> 80-100 FL ✓ Normal RDW >> 11.5-15% ✓ Normal MCH >> 29±2 picograms ✓ Normal Ferritin >> 12-150 in females 12-300 in males Case One …..continuation Lab: Hb 8, MCV 72, RDW 19, MCH 20pg. WBC 8000/Normal dif.Plts 380000 Bld Film: microcytic, hypchromic, anisocytosis, poikilocytosis, Retics (corrected) o.8% Serum Ferritin 2 Spooning of the nails (koilonychia) Angular cheilitis >> Upon Esophagogram and endoscopy the patient was found to have Esophageal web ✓Esophageal web + Dysphagia + IDA >>> Plummer-Vinson syndrome (PVS) Hb Electrophoresis?? Serum B12, Folate?? S Fe, TIBC??, BM ??? GI endoscopy??, Investigate for bleeding disorder: VWD?, celiac disease? Gyne consulation GI consultation Treatment/ Follow up of Case 1 1‐ Oral Iron: Fe gluconate, sulphate 2‐ educate 3‐ IV Fe?? Fe sucrose/carboxymaltose or new Fe dextran Follow up: check CBC every month : expected Hb rise ± 1g/ 10 days. Check Ferritin at 3 months. Follow other investigations and consulations Differential Diagnosis of Microcytic Anaemia • Thalassaemia syndromes • Certain haemoglobinopathies (Hb C) • True (classical) iron deficiency secondary to blood loss, iron‐poor diet, increased iron needs, Helicobacter pylori infection or gastric pathology • Anaemia of chronic inflammatory diseases • Certain forms of sideroblastic anaemia • Genetic forms of iron deficiency anaemia Two B Case one 60 yr old male complains of :Dizziness, Fatigue, Shortness of breath especially on exertion and Headaches for the last 2 months. He has constipation and weight loss 5 kg over 2 months. Lab: Hb 8, MCV 72, RDW 19, MCH 20pg. WBC 8000/Normal dif.Plts 380000 Bld Film: microcytic, hypchromic, anisocytosis, poikilocytosis, Retics (corrected) o.8% Serum Ferritin 2. FOB x 3 positive in 2. Case One B Angular Chelittis & Glossitis Findings: after doing Colonoscopy > biopsy > histology Diagnosis: Colon adenocarcinoma Mod. dif. causes chronic blood loss > IDA Always Look for a cause for IDA. Anemia must have a full identification koilonychia Anemia is not a final diagnosis IRON DEFICIENCY ANEMIA IS NOT A DIAGNOSIS PER SAY. ALWAYS PUT A LABEL TO IT: IDA DUE TO UPPER GI BLEEDING DUE TO GASTRIC CANCER

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