Hct is 3x the Hg so think Hb 15 Hct 45 in men.
Hct above 30 no symptoms. 25-30 feel tired. 20-25 dyspnea
You die from coronary ischemia with anemia.
High MCV: Megaloblastic is macrocytic anemia with hyper segmented neutrophils. Only B12 and folate deficiency would cause Megaloblastic. Alcohol, liver disease and some drugs can cause macrocytic anemia but not megaloblastic.
Low MCV: iron deficiency, thalassemia, and siderblastic anemia cause microcytic anemia.
Normal MCV: acute blood loss. Not enough time to change size of blood cells, so normocytic. Instead, you find lots of reticulocytes as bone marrow tries to compensate by making lots of immature RBCs. Normal MCV is 80-100.
There is a limit on how much iron you can absorb per day so pregnant women who are anemic can take a lot of iron, but only a limited amount of it will be absorbed, so they often stay anemic, even with iron tablets.
You excrete a constant amount of iron per day, and that amount cannot increase. Because of this, people with thalassemia who get lots of transfusions often have iron overload, leading to hemochromatosis, and they can’t get rid of that extra iron from the packed RBCs they get twice a week. You shouldn’t treat them with phlebotomy because you don’t want to drain the blood they just got transfused with. So instead, you treat the iron overload with deferoxamine.
Microcystic anemia associated with colon cancer. If patient over 50, do colonoscopy!
Sideroblastic anemia from defective heme synthesis, causing iron to form ring around mitochondria in premature RBCs. Caused by b6 def needed in ALA Synthase in heme formation, x-linked defect in ALA Synthase, or lead poisoning which inhibits ALA Synthase. Alcohol most common cause of sideroblastic anemia. If caused by alcohol or lead, remove it. If caused by genetic defect in ALA synthase, treat with pyrodoxine (B6).
Thalassemia most likely see target cell in smear.
Iron def anemia most likely see increase in RDW — rbc distribution width – all different sizes, bc new cells deficient in hemoglobin — smaller.
How to distinguish Iron def anemia from other microcytic anemias like sideroblastic and thalassemia? It is only microcytic anemia where u see decreased ferritin (storage form of iron), best initial test. But ferritin can go up during stress so shows as normal in 1/3 pts. Therefore also test for TIBC (total iron binding capacity) to see how much empty seats RBCs have. TIBC will go up in Iron def anemia. Ferritin levels best initial test but most accurate is bone marrow biopsy (but invasive, so not common, only do last)
how to distinguish sideroblastic anemia from other microcytic anemias? Only one with increased iron in blood, because can’t incorporate into heme.
Fastest and most effective way to replace iron is via blood transfusion. But if you are not in an emergency, you can use oral ferrous sulfate, but since it’s 98% not absorbed, you poop most of it out and turns your poop black. If the patient is Jehovah’s witness and refuse transfusion but needs iron quickly, use intramuscular iron.
Prussian blue stain stains the iron around the mitochondria in sideroblastic anemia… Diagnostic.
96% of your hemoglobin is HbA = 2alpha + 2 beta chains.
2% is HbA2 = 2alpha + 2 delta.
2% is HbF = 2alpha + 2 gamma.
In alpha thalassemia, no alpha chain so HbA, HbA2, HbF all decrease in equally proportional amounts. In beta thalassemia, no beta chain so HbA decrease but HbA2 and HbF have proportionally larger amounts according to electrophoresis. Diagnostic.
Alpha thalassemia: delete 4 genes is Hb Barts. Cause hydrops fetalis. Delete 3 genes is HbH, moderate disease. 2 genes is mild. 1 gene is asymptomatic.
Alcohol-induced anemia no hypersegmented neutrophils vs B12/folate def have hypersegmented neutrophils (megaloblastic anemia). See on smear – diagnostic. Both cause same symptoms of dementia, neuropathy (folate no neural problem), and myopathy.
Folate deficiency from either decreased intake or rapid DNA material turnover like in sickle cell or psoriasis. B12 def usually not from decreased intake bc we have big storage. Most commonly caused by pernicious anemia. Diphyllobothrium latum-caused B12 deficiency is rare.
B12 levels sometimes normal even if we are deficient, bc transcobalamin (B12 transporter) is acute phase reactant that is released during stress. Therefore better test B12 def w methylmalonic acid levels. Best test for etiology is to detect anti-intrinsic factor and anti-parietal cell antibodies. If this is neg, then do Schilling test.
In B12 def, you can have either neuropathy, macrocytic anemia, or both.
Intravascular hemolysis — increased reticulocyte, LDH, and bilirubin. Decreased haptoglobin, which carries hemoglobin to liver, spleen, and bone marrow to get recycled. You see this in hereditary spherocytosis, autoimmune hemolysis, paroxysmal nocturnal hemoglobinuria, and sickle cell.
Intravascular hemolysis — dark urine from free hemoglobin, NOT bilirubin, which is unconjugated (indirect, bound to albumin, can’t get excreted in urine).
Sickle cell see sickle cell in smear. If just trait, won’t see it. However electrophoresis most accurate diagnostic test.
Give antibiotics in sickle cell pts with fever or high wbc count bc they have no spleen. Dont wait for cultures to come back. If you wait any longer, they could die.
Pt w hemoglobinopathy like sickle cell who have sudden decrease in hct, suspect parvovirus b19 bc attacks reticulocytes. Rx IV immunoglobulins.
Sicke cell crisis ( ie visual disturbance, chest pain, CVA, CNS disturbance, etc) rx exchange transfusion — converts them from homozygous to like heterozygous. Normal RBC will provide enough oxygen to prevent sickling.
Sickle cell pt — give hydroxyurea to decreases chances of sickle cell crisis. Also give folate bc chronic hemolysis, and pneumococcus vaccine to supplement weak spleen.
Autoimmune hemolysis – suspect if pt has other autoimmune diseases like lupus, cll (abnormal lymphocytetes make autoimmune antibodies), rheumatoid arthritis. Also suspect if pt taking penicillin, methyldopa, or quinidine bc these drugs provoke autoimmune response. Test with coombs reagent see aggregation. Rx w steroids. If symptoms keep reoccurring, get splenectomy so RBCs won’t get destroyed.
Hereditary spherocytosis is recurrent (bc hereditary) and spleen gets big. Blood cell gets to round to squeeze through the vessels in the spleen. Blood cell hemolyze. Rx get splenectomy so RBCs won’t keep getting destroyed.
Paroxysmal nocturnal hemoglobinuria from lack of DAF, which prevents complement on own cells. RBCs become extra sensitive to pH, and lyse. DAF aka CD55 & CD59. Test for these to diagnose. Can also use sugar water test. Most common cause of death is large vessel thrombosis, but cause unknown. Rx w steroids.
G6PD deficiency. See Heinz body which is oxidized hemoglobin. Macrophages bite them out so see bite cells. In acute setting, G6PD will be normal. Gotta wait few months before testing G6PD levels. Most common cause of onset of symptoms is not primaquine or fava beans, but infections (oxidizing stress). Rx by avoiding oxidating stress.
Aplastic anemia you see all cell lines down in CBC, then do bone marrow biopsy to rule out cancer, lupus, etc. If you are under 50 and have bone marrow match, then do bone marrow transplant. If over 50 and no match, then rx w cyclosporine or antithymocyte globulin (ATG).
AML more in adults. ALL more in kids. Have same symptoms of anemia and infections (wbcs not fxnal). Hw do we know it is leukemia vs infection?we see blasts (ALL lymphoblastic, AML myeloblastic). To distinguish between the blasts, use monoclonal antibodies. You can also use stains: AML pos for myeloperoxidase and Auer rods.ALL is pos for CALLA (Common ALL Antigen). AML treat with daunorubicin, ara-c. But, also treat M3 AML (promyelocytic, PML, 15;17) w all trans retinoic acid, to help cells grow up, differentiate. ALL rx w daunorubicin, vincristine, prednisone.
First round of chemo removes 99.99% of cancer cells — remission induction.
Second round removes another 99.99% — consolidation therapy.
Third round — maintenance therapy.
Do cytogenetic testing to see if can do bone marrow transplant. If genetically you have high chance of relapse, then you should do bone marrow transplant before you relapse. Otherwise, just stick w chemo, bc bone marrow transplant has night mortality (20%).
Autogeneic bone marrow is from self. Best bc no rejection, but chance that you’ll get some cancer cells. Allogeneic second best but can get rejection. Less related = more time that you’ll be neutropenic, get infections. Give intrathecal methotrexate to prevent cancer from coming back to spine, bc start in spine.
You can also get leukophoresis.
Acute leukemias – pt usually die in 10-12 wks.
Chronic leukemias – pt usually die in 10-12 yrs.
Chronic leukemias are much better than Acute leukemias because the WBCs are at least working and can fight off infections.
End stage CML treat with fludarabine. Used to use chlorambucil, but doesn’t help in stopping disease or lowering mortality. If Coombs test pos, also use steroids (autoimmune hemolysis)
CML have over 90% neutrophils. CLL have over 90% lymphocytes.
Leukemoid reaction looks like leukemia in that there are increased WBCs but unlike leukemia, the Leukocyte Alkaline Phosphatase (LAP) is increased bc the WBCs are functioning. Caused by infection, when you have a lot of WBC to fight off infection
Dx CML w low LAP and pos for Philadelphia chromosome.
CML more likely than CLL to spread to spleen, so you get splenomegaly, pressing against your stomach, causing abdominal pain and early satiety when you eat. 20% CML progress to AML, called Blast Crisis. You want to treat the CML before it has blast crisis and becomes AML.
Imatinib best rx for CML, because it stops Philadelphia chromosome from producing tyrosine kinase (bcr-abl). Hydroxyurea is next ( inh RNR — decrease cell prolif, but doesn’t stop problem). Only bone marrow transplant most likely cure.
Don’t do Allogeneic bone marrow transplant over age 50. This means most CLL pts won’t get it because they tend to be older. Don’t do autologous transplant after 60. And don’t do stem cell after 70.
Plasma cell leukemia, multiple myeloma make monoclonal IgG and IgA antibodies (M spike) against “imaginary enemies” rather than other infections you’re supposed to fight, so u get lotsa infections. See more than 10% plasma cells! It also releases Osteoclast Activating Factor (OAF) causing your bones to get resorbed, causing bone pain… most common complaint. It also releases light chains of Ig (Bence Jones protein) that is toxic to renal tubules, causing renal insufficiency. Increased plasma cell turnover causes hyperuricemia from the Plasma cell DNA (uric acid from breakdown) that gets destroyed. You don’t get hyperuricemia from hemolysis bc RBCs have no nucleus. Plasma cell tumors take up space in bone so it can’t make other stuff as much, causing anemia.
In multiple myeloma, the hypercalcemia, Bence jones protein, uricemia all kill the kidney, cause amyloidosis.
Testing for plasma cell count is the best diagnostic test for myeloma.
If plasma cell is high but have no symptoms of bone pain, infections, kidney failure etc, then its just MGUS — monoclonal gammopathy of undetermined significance. Only 1% proceed to become multiple myeloma.
If less than 70, rx mm w autologous stem cell transplant. Only short neutropenic period. Chemo rx vincristine, adriamycin, dexamethosone to prepare for transplantation. If over 70 and healthy, rx chemo thalidomide. If over 70 and weak, rx melphalan, which is palliative.
Unlike swollen lymph nodes in infections, lymphomas are not red, tender, warm, or swollen. Do excisional biopsy (take whole thing out) for dx. If stage I or II, rx w radiation. If stage III or IV, rx w combination chemo (systemic) which has ae and risk of leukemia.
Stage I have 1 lymph node group effected.
Stage II have 2 lymph node group effected.
Stage III have lymph node groups on both sides of diaphragm. Systemic, or have fever, wt loss, night sweats (B symptoms).
Hodgkin rx ABVD – adriamycin, bleomycin, vinblastine, dacarbazine
Nonhodgkin rx CHOP – cyclophosphamide, hydroadriamycin, oncovin (vincristine), prednisone.
Most ppl w hodgkin in stage I or II so radiation is often all you need. Safer, bc no ae of chemo — cardiomyopathy of adriamycin, pulm fibrosis of bleo, neuropathy of vinblastine.
Most ppl w nonhodgkin in stage III or IV, so often need chemo. Biggest ae of CHOP is infertility. Chemo also has risk of leukemia. Also can use rituximab bc is mab ag cd20, overexpressed in nonhodgkin lymphoma.
Platelet bleeding is more superficial, like on mucosa, gums, skin, epistaxis, petechiae. Factor bleeding is deeper, like into muscles, joints, hematoma.
Increased aPTT and normal PT think hemophilia (def VIII or IX, intrinsic, only in male), Von Willebrand disease (Remember vWF carries Factor VIII), and Lupus (but presents w thrombophilia rather than bleeding!!)
Isolated low platelets (less than 50,000) in healthy pt w normal spleen = ITP. Is low platelet due to production problem? Check megakaryocyte levels. If normal, then production fine. ITP often find anti-platelet antibodies (but not specific bc common). Rx w steroids. If keep recurring then get splenectomy (platelets sequestered in spleen). If life threatening bleeding (from lack of platelets), give IVIG/Rhogam, full of Immunoglobulins. The immunoglobulins swamp the macrophages so that less platelets+antibodies are gobbled up by them.
Factor XI and XII deficiency increases aPTT (intrinsic) but rarely if ever causes bleeding (maybe bc early in intrinsic pathway?).
Hemolytic Uremic Syndrome (HUS) is when ur missing the enzyme that breaks down vWF (metalloproteinases like ADAMTS13). Your clots stay put instead of disintegrating. RBCs slam into clot and break up into schistocytes, particularly in small blood vessels, and you get microangiopathic hemolytic anemia. Does same in kidney and cause uremia (leaking of nitrogenous waste into blood). You have low platelets.
Thrombotic thrombocytopenic purpura (TTP) is HUS w CNS sx and fever.
Rx HUS and TTP w plasmapheresis to replace the missing metalloproteinases so that you can break down vWFs.
HUS and TTP — too much vWF due to lack of metalloproteinases.
vWF Disease — either too little vWF or dysfxnal vWF. Test fxn w ristocetin test. Ristocetin is fake endothelium. Test to see if vWF can aggregate on the ristocetin. Rx vWD w DDAVP (desmopressin), which causes endothelium to release vWF and Factor VIII.
In both hemophilia and vWD see normal platelet count, increased aPPT and normal PTT.
In hemophilia you will see normal platelet count, bc problem is w the fibrin (via factors), which stabilizes clots after a day. So you get delayed clotting time. In vWD also see normal platelet count.
Rx mild hemophilia and vWD w DDAVP bc release VIII (and vWF).
Rx severe hemophilia and vWD by replacing missing factor (made in programmed ecoli)
DIC see elevated d-dimers and fibrin split products, which are split off from fibrinogen to form fibrin. Shows lotsa clotting. D-dimers are the chopped up fibrin part after dissolution of the fresh fibrin by plasmin. Show lotsa declotting.
Plasmin only destroys fresh fibrin (before XIII crosslinking). 3 hrs after stroke or 12 hrs after infarction, XIII crosslinks fibrin, making it strong and resistant to plasmin.
DIC rx w FFP and platelets to replenish factors. Ppl usually present w DIC when bleeding so don’t give heparin!
Only 3 things will increase both PT and aPTT while keeping platelets normal: DIC, liver disease, and Vit K def. If giving Vit K improves sx, then u know bleeding is due to Vit K def. otherwise, from liver disease. rx w FFP.
Thrombophilia: Lupus (high aPTT w thrombus diagnostic!), Factor V Leiden and ATIII Deficiency (low aPTT). Factor V Leiden most common thrombophilia!