Taking The Fear Out of Abnormal CBC s Problems of Production, Destruction or loss

Transcription

1 Taking The Fear Out of Abnormal CBC s Problems of Production, Destruction or loss Joanne Eddington, MN, FNP, AOCN Providence Oncology and Hematology Care Clinic - Eastside

2 Blood Cell Abnormalities Abnormalities of production Parts? Factory? Abnormalities related to loss Bleeding? Sequestration? Abnormalities related to destruction Autoimmune/Idiopathic?

3 Variables to focus on Hgb and Hct MCV RBC distribution width (RDW) Platelets WBC with differential Patients baseline, differences based on sex and race. If abnormality exists out of context, repeat the test.

4 Coulter counter Counts circulating blood cells by electrical pulse The height of the pulse indicates cell volume Newer counters give multimodal assessment of cell size and content which is the differential. 5 part differential includes neutrophils, lymphocytes, monocytes, eosinophils and basophils

5 Stick The Tube In The Machine- And Let IT Do Magic Automated Hematology Analyzer 2 CHAMBERS In one chamber, the red cells are counted. The detecter is set to count merely the cells the size limits of Red Blood Cells. In the other chamber, the blood is put into a solution that lyses the red blood cell leaving merely WBC and platelets intact.

6 Approaches to evaluation History Physical exam Review of differential and peripheral smear as appropriate Additional tests as appropriate Depending on results, Hematology referral.

7 Platelet Abnormalities

8 Thrombocytopenia Definition: Platelet count < 150,00 Asymptomatic Thrombocytopenia Found on routine CBC Symptomatic Thrombocytopenia Bleeding, bruising or petechiae

9 Thrombocytopenia Decreased platelet production Viral infection, HIV, Hep C, Parvovirus Leukemia, Vitamin deficiency Increased Platelet Destruction Drugs: Heparin, Valproic acid Autoimmune destruction ( TTP, ITP, Lupus) DIC Platelet loss / Psuedothrombocytopenia Platelet clumping (EDTA induced), Pregnancy Splenic sequestration

10 Critical Values Surgeons will generally consider platelet number to be adequate if >50,000 Spontaneous bleeding does not occur unless platelet count is < 20,000 Transfuse platelets if <10,000 or spontaneous bleeding

11 Laboratory evaluation for Thrombocytopenia CBC with manual differential, PT/PTT and review of Peripheral smear Evaluate for drug induced thrombocytopenia and hypersplenism Abdominal ultrasound Rule out HIV infection, lymphoproliferative disorder and autoimmune disease. HIV testing, ANA and SPEP

12 Points to remember. TTP/hemolytic uremic syndrome need urgent therapy. Idiopathic thrombocytopenic purpura is a diagnosis of exclusion. ITP: less likely to bleed spontaneously as platelets are often young and vigorous! Bone Marrow biopsy or platelet antibody tests are not indicated in most work-ups of ITP. It is appropriate to initiate work-up but most situations should be referred to Hematology.

13 Thrombocytosis Marrow over production Myeloproliferative disorder Can be a result of something else going on (Reactive Thrombocytosis) Seen in iron deficiency Seen in post surgical patients Seen in infection Seen in trauma

14 Thrombocytosis Defined as >450,000 but evaluation is not necessarily indicated unless near 600,000 Primary Thrombocytosis versus Reactive Thrombocytosis Elevated platelet count can be due to a myeloid malignancy or myeloproliferative process Elevated platelet count can be due to a secondary process such as: Iron Deficiency Anemia Infection/Inflammation/Tissue Damage Hemolysis Nonmyeloid malignancy Splenectomy

15 Thrombocytosis continued The difference between primary thrombocytosis and reactive thrombocytosis is clinically relevant because primary thrombocytosis is associated with increased risk of thrombohemorragic complications and reactive thrombocytosis is not.

16 Clinical evaluation of Thrombocytosis Patient History Old medical record will determine if a new or longstanding problem Splenectomy? Chronic thrombocytosis in patients with a spleen is highly suggestive of primary thrombocytosis. Chronic thrombocytosis in patient without a spleen is a benign condition.

17 Laboratory evaluation CBC Increased HGB, MCV or WBC or immature WBC, suggests Primary Thrombocytosis/Myeloproliferative disorder Serum Ferritin Rule out iron deficiency C-Reactive Protein Elevation indicates an inflammatory cause Normal levels are seen in a marrow disorder

18 If no cause can be found for a reactive process, refer. Hematology evaluation will likely include: JAK 2 testing Bone Marrow biopsy Bcr/Abl

19 Primary Thrombocytosis Myeloproliferative disorders Essential Thrombocytosis Polycythemia Vera Primary Myelofibrosis Myeloid Malignancies MDS CML

20 White Blood Cell Abnormalities

21 Leukopenia/Neutropenia Leukopenia refers to a low total WBC Granulocytopenia refers to a decrease in circulating neutrophils, eosinophils and basophils Neutropenia refers to a decrease in circulating neutrophils ANC or absolute neutrophil count = Total WBC x percent (polys + bands) / 100

22 Points to remember Patients with moderate to severe neutropenia will not demonstrate classic signs of infection other than fever. Ethnic variations: African Americans, Yemenite Jews, Ethiopians and certain Arabs normally have a slightly lower WBC and ANC. Benign Ethnic Neutropenia (ANC not <500)

23 Acquired vs congenital Neutropenia Congenital neutropenias are rare Acquired causes: Drugs or infections (virus, sepsis) are more common Immune disorders: HIV, Chronic Idiopathic Neutropenia Leukemia or other hematologic malignancies rarely present with isolated neutropenia

24 Lymphopenia Often caused by immune suppressive drugs including steroids and antilymphocyte monoclonal antibodies HIV Critical illness Connective tissue diseases Lymphopenia seen in elderly patients, where it is usually of no clinical significance. No further investigation is advised in an elderly patient with a lymphocyte count > /L in the absence of any concerning symptoms Persistent lymphopenia that remains stable over a six month period and in the absence of symptoms, clinical findings, or abnormal results from investigations does not require further investigation

25 Diagnostic Approach If leukopenia, neutropenia or granulocytopenia is identified along with other blood abnormalities such as normocytic anemia and/or thrombocytopenia, a peripheral smear and an immediate referral to a hematologist for a bone marrow biopsy should be done. Mild neutropenia without recurrent infections or protracted infection can be observed.

26 Diagnostic Approach cont If observation is appropriate ANC should be checked at least 2-3 times per week for 6-8 weeks. If neutropenia persists, refer to Hematologist for a bone marrow biopsy and further evaluation. Moderate to severe neutropenia with infection should be referred directly to Hematologist for bone marrow biopsy and further evaluation.

27 Leukocytosis First step in evaluation is to determine which WBC type is increased. The increase maybe secondary to immature precursors (blasts) or an expansion of mature leukocytes such as granulocytes, lymphocytes, monocytes. Manual differential and review of peripheral smear will help classify and rule out acute leukemia.

28 Leukocytosis Total WBC > 11,000 Leukocytosis commonly is due to an increase in the number of circulating neutrophils Leukocytosis can also be due to an increase in other white blood cell such as lymphocytes, eosinophils, monocytes or rarely basophils.

29 Causes to consider: Normal variation By definition 2.5% of the population will be greater than 2 SD above the mean Blood sampling problem Platelet clumping Infection or inflammation Total WBC + CRP + Neutrophils Drugs Bone Marrow disorder

30 Specific differential abnormalities Neutrophilic leukocytosis: infection, stress, smoking, pregnancy, PV and CML Lymphocytic leukocytosis: Infections such as mono, ALL, CLL, NHL Monocytic leukocytosis: Acute bacterial infections, TB, AML and CML/MDS Eosinophilic or basophilic leukocytosis: paracytic infections, allergic reactions, solid tumors, forms of chronic and acute leukemia's (HES)

31 Red Blood Cell Abnormalities

32 Anemia's Various definitions (hemoglobin and hematocrit levels) < 12 in women and < 14 in men Production problems, destruction problems or loss Classification: Normocytic, Macrocytic, Microcytic

33 Anemia Parameters Print out from out from machine RBC counted (coulter) HB measured (light abs) MCV from size distribution

34 Initial questions to ask: Is the patient bleeding? Is there evidence for RBC destruction/hemolysis? Is the bone marrow suppressed? Is there iron deficiency? If so why? Is there B12 or folate deficiency? If so why?

35 Initial test to order Complete Blood Count with differential Iron studies with ferritin B 12 and Folate Reticulocyte count CMP (creatinine, total protein, LFT s) TSH Additional studies depending on these results.

36 What Test Tells Production v Destruction? Reticulocytes Reticulocytes are immature red blood cells, typically composing about 1% of the red cells Reticulocytes mature in bone marrow and then circulate for about a day in the blood stream They are called reticulocytes because of a reticular (mesh-like) network of ribosomal RNA that becomes visible under a microscope with certain stains such as new methylene blue This test must be ordered separately Modern instruments can automate the process

37 Microcytic Anemia Definition: MCV < 80 Caused by: Iron deficiency Thalassemia Chronic disease Serum ferritin should be the first test to check as part of initial work-up. Iron deficiency is unlikely in the presence of persistently normal or elevated serum ferritin.

38 What do you see? Microcytosis and increase in RDW Classic Iron deficiency anemia MCV= 72

39 Iron Deficiency Anemia (IDA) Most common form of anemia Should be ruled out initially in every anemia workup. Can see iron deficiency combined with other types of anemia # 1 cause of iron deficiency is bleeding The cause of bleeding should be sought in every case.

40 IDA continued Always trial oral iron unless patient has documented absorption problem Parenteral iron can replenish iron stores in 1 dose. But not risk free. Standard of care is to replace iron stores. Don t transfuse. Note- it will take 1-2 mos for HB to rise, be patient If patient is bleeding, stop the bleeding first as they will not retain the iron you give them!

41 Thalassemia This should be considered if patient is microcytic but not iron deficient. Patient can have Thalassemia and IDA. Iron deficiency must be corrected before testing for Thalassemia. History is very important in identifying Thalassemia Don t give iron unless iron deficient. Use Hematologist to interpret Hgb electrophoresis

42 Microcytic anemia of chronic disease Otherwise known as anemia of inflammation These are anemias of Chronic Inflammatory diseases, like RA. THIS IS NOT CHF, HTN, DM which are chronic diseases, not characterized by inflammation Usually iron studies demonstrate: Low serum iron, low total iron binding capacity and increased serum ferritin. However, ferritin could be elevated by inflammatory process itself. Bone marrow biopsy maybe necessary to rule out iron deficiency.

43 Macrocytic Anemia Definition: MCV > 100 Caused by: B12 or folate deficiency (consider MMA levels) Hypothyroidism Hemolysis (consider LDH and Direct Coombs) Myelodysplastic syndrome Alcoholism, liver disease Medications

44 Macrocytic anemia continued Once the cause is determined, appropriate treatment can then be administered as indicated. Hematology evaluation is indicated if MDS or hemolytic anemia is suspected.

45 Normocytic Anemia MCV Caused by: Bleeding Renal insufficiency Hemolysis (valve, TTP/HUS, DIC, autoimmune, etc.) Nutritional deficiency (yes iron, B12 and folate) Bone marrow disorders Anemia of Chronic Inflammation (here too- both micro and normo cytic )

46 Normocytic anemia If the work-up excludes bleeding, nutritional deficits, renal insufficiency, hemolysis, then the anemia is related to chronic disease or a primary bone marrow disorder. Evaluation for hemolysis: Schistocytes or spherocytes on smear Haptoglobin, Lactate dehydrogenase (LDH), Direct coombs, indirect bilirubin, and reticulocyte count. Consider drug-induced.

47 Polycythemia Suspected when Hgb and Hct are elevated. Primary Polycythemia (Polycythemia rubra vera; PV) Is a myeloproliferative disorder of the bone marrow. Secondary Polycythemia Caused by increased EPO levels due to hypoxia or an EPO producing tumor. Relative Polycythemia Caused by a decreased plasma volume increasing Hgb, Hct and RBC count.

48 Laboratory evaluation of Polycythemia Carboxyhemoglobin levels Elevated in smokers Erythropoietin levels Elevated Suggests erythropoietin producing tumor Low is characteristic of Polycythemia Vera JAK 2 testing Diagnostic for Myeloproliferative Disorder and Polycythemia Rubra Vera.

49 In summary If the patient feels sick and has abnormal blood counts..be worried and refer. If the patient has more than 1cell line abnormal even if they don t feel bad.be worried and refer. If the laboratory result does not fit with the clinical situation, recheck. Consider running CBC in heparin instead of EDTA.

50 In Summary continued If the patient has mildly low abnormalities and feels fine..consider watching and waiting. Pay attention to the work-ups that your friendly hematologist does on your patients. This will improve your initial work-up overtime.