Transcript for:
Hematological Manifestations of SLE

uh good morning to everybody who's joined and welcome to the first rheumatological presentation for the year it's going to be done by dr ivyanafi a fellow in the department of rheumatology she's going to discuss the hematological manifestations of sle this is quite a huge and broad topic and it's going to be hopefully done very well by her title is a bloody attack similar to the bloody mess we rheumatology in the charlotte mckexie but i'm sure she'll do well in her presentation ivy thank you thank you professor one um good morning everyone and welcome to um this presentation thank you for tuning in my name is dr ivia nefe and i'm a fellow in the department of rheumatology at johannesburg academic hospital the title of my talk is a bloody attack and we'll be looking at the hematological manifestations of systemic lupus erythematosus as paul solomon said this is quite a broad topic but i've tried to make it brief and i'll summarize as much of the manifestations in this time that we have so the outline of my talk um is going to be as follows first we have a few i have a few case discussions that we'll be going through and then we'll look at the spectrum of hematological abnormalities seen in sle and how to manage them then we'll look at the implications of these hematological abnormalities with the sle disease process and also talk briefly about uh the south african experience so uh the first case uh is that of a 35 year old female um she presented to one of our satellite hospitals with uh with symptomatic anemia severe symptomatic anemia with no um evidence of the sort of a source of bleeding she had she was transfused and on wake up fbc shows her first um fbc that she presented with you can see she's got a normocytic anemia and post-transfusion the hp improved to 8.8 she was discharged to come back for an endoscopy because her hematitic screen was normal and they couldn't find the source of bleeding then um she presented again in a few weeks this time around one of our consultants was covering the satellite hospital and the anemia had recurred so that's nbc3 that you can see on the screen she had a severe pneumocytic anemia but note the mcv is quite on the high side of normal the blood cells look macrocytic and she also had a thrombocytosis renal function was normal so this prompted them to do a peripheral blood smear because there was a suspicion of possible hemolysis here and the blood smear showed um spherocytes and fused schistocytes she was hiv negative and to confirm the hemolysis she had a raised ldh and reduce heptoglobin and reticulocytosis we went on to do a kum's positive coombs test for hair sorry and it came back positive for both um immunoglobulins and complement c3d so um with a presentation there was a suspicion that there was probably an autoimmune cause for this hemolysis so we screened her for as sle and her a a and double-stranded dna came back positive she was managed for the hemolytic anemia and referred to our clinic at jobeck gen for follow-up and when she came decided to do a full workout for uh sle because we noticed she had proteinuria and an active urine sediment and uh class iii lupus nephritis was confirmed on renal biopsy the second case as a patient was known to the hematology department some time ago who presented to them with itp so she came in the first time it's king bruising and it is taxes and a bi-cytopinea with anemia and thrombocytopenia she had reduced platelet numbers on a peripheral smear and had a bone marrow done that she would increase mega cary side she was hiv negative so she was being managed by hematology she was on steroids and also on acetoprint and because of the refractive nature of her itp she subsequently under underwent a splenectomy and possibly anatomy she developed the dvt and was readmitted it was at that point that they noticed she developed synovitis on admission and rheumatology was asked to review her so um we decided to do an autoimmune workup and she came back positive for anti-nuclear anti-antibodies um anti-smith antibody and double-stranded dna she also had hypocomplementaemia we decided to screen her antiphospholipid syndrome because of the dvt even though it was quite obvious that it was provoked from the surgery and that was negative this patient also two years down the line developed liposnephritis and then the third case is a patient who came in with um a bicycling as well severe thrombocytopenia with an anemia with deranged renal function and the normal inr a smear was sent and she had numerous fragments on the smear with a raised ldh she was hiv negative on admission she was not noted to have alopecia and a dearly rash so um the suspicion of sle was made and black serologic confirmed that she had an ana positive she was a ana positive double-stranded dna positive and she also had hypercomplementemia post treatment with plasmapheresis and steroids she had four blood counts normalized and her aki had acute kidney injury also resolved um the last case i'll talk about is of a young patient who um had ex had recurrent and provoked um deep vein thrombosis so she had one uh dvt in the left leg that was treated in the periphery for six months on warfarin and then two months after stopping her treat after completing her treatment she had another dvd in the right leg that's when she came to um joe beck jen and before we started anti-calculation before anti-coagulation was started the doctor who saw her then decided to screen her for possible antiphospholipid syndrome and she was positive for both anticardiolype and antibody and glucose anticoagulants um so we did a full uh autoimmune recap for her sorry the doctor who saw her then did a full autoimmune wake up for her and she was a ana positive and anti-double-stranded dna because the band was put on lifelong warfarin after about three years she probably had compliance fatigue and stopped her warfarin and then she came back a year after with a new dvd in her right leg this time with a pe she's currently and boyfriend was restarted before i was restarted we decided to repeat her antiphospholipid antibodies and the acla was positive again so she's now on lifelong warfarin and unfortunately he has also developed a class for lupus nephritis down the line so um having gone through these cases it's quite obvious that um hematological abnormalities are quite common in sn before we go into um we go more into that i'll just take us briefly through the history of sle and we can divide this into three periods the classical period the new classical period and the modern era so the classical period which dates back to about the 13th century lupus was seen mainly as a cutaneous disease and and what they recognized was this rash on the face of the of the of the patients and one a physician called rogerius termed the the came up with the term lupus because he thought those lesions resemble the bite of the wolf and both in latin and lupus so it was mainly seen as a dermatological problem until the 19th century in the neoclassical period where kaposi realized that this skin rash was associated with other systemic disease and abnormalities in the blood the hematologic the hematological abnormalities um abnormalities were also seen their blood wasn't spared and now we've moved to the modern era from the 20th century where we've been able to link um sle immunology and we've discovered several auto antibodies associated with it including the discovery of the early cell the bone marrow so um what causes sle the the exact uh athletogenesis is not known but we know that as a multi-system immune detect inflammatory disorder and there's an interplay among genetic factors hormonal factors and environmental factors and we also know that there's immune dysregulation and autoimmunity the the the hallmark of the pathogenesis that there's um this dysfunction of about t and b cells and also there's complement deficiencies and there's abnormal cytokine production with autoantibodies formed to the various cell nuclear components which we call the antinuclear antibodies a a um when um cells become when cells apoptosis or the cells die and they release cell debris in sll's we notice that the phagocytosis and the clearance of these cells is not optimal so you have a lot of circulating apoptotic cells which um which the body recognizes as antigens so um the antigen presented cells see these cells and present them to the um to the um immune cells which subsequent the t and b cells which are not functioning normally and they produce um auto antibodies to these self antigens and these antibodies and the antigens from complexes which we call immune complexes and as they circulate through the system they deposit in various organs and because there's loss of immune tolerance there's chronic inflammation and the and and tissue damage as a result of this deposition so this is a cartoon um that diagram that i sourced from a sage publication which shows the pathogenesis you can see uh from the top left corner the um the apoptotic cells that are not being cleared efficiently and the antigen presents ourselves then this cells pig sees them as antigens and stimulates the t and the b cells to produce cytokines and antibodies they form complexes and deposits on the on the membranes of various tissue causing damage we also look briefly at how to make a diagnosis of sle so the select criteria which is the systemic glucose international collaborative clinic criteria is the one that we commonly use it's consists of 17 features 11 of which are clinical criteria and six immunologic criteria and to make a diagnosis of sle you need at least four criteria one of which must be a clinical criteria and one should also be a laboratory criteria and under the clinical criteria you can note the some of the hematological abnormalities shown there hemolytic anemia bucopenia and a thrombocytopenia and also you've got antiphospholipid coming up under the immunologic criteria and a direct coums test which you will consider if there isn't already hemolytic anemia as a clinical criteria just to mention there is a new criteria that has been developed by eula and acr american college of rheumatology um since 2019 and this criteria um seems to wait weights the different manifestations of sle so there are six um there are 10 domains and under these domains there are different features which um are weighted so for you to make a diagnosis of sle the entry criterion is that you should first have an a and a positive titer of at least 80 and then you weight the different features that the patient has and if the patient has a total score of at least 10 then you can make a diagnosis of sle and note that there is a domain here also for hematologic abnormalities uh leukopenia thrombocytopenia and autoimmune hemolysis and the immunology domain that is antiphospholipid antibodies so let's zoom into the spectrum of hematological abnormalities um there are chromatological abnormal disorders are common in sle and um they occur at various times some of sometimes they are seen months or years even before the full-blown presentation of sle or they may be seen at the initial presentation of sle or they may occur during the course of their disease they can be immune mediated with the same mechanism of the sle or there may be a complication of the disease example um if you have a patient with lupus nephritis and they develop anemia it's as a result of the complication of the disease and and a few times we also see them as a complication of the treatment that we give which are immunosuppressants and sometimes chemotherapy and they're grouped mainly into the calculopathies and the cytopenias under the coagulopathies we have antiphospholipids syndrome as a big one and the cytopenias can affect any of our cell lines so we can have anemia leukopenia which may be neutropenia or lymphopenia and then from thrombocytopenia and there are various causes of anemia in in sle and i've grouped them into the immune mediated ones and the non-immunitated ones with immune-mediated um anemia and sle it may be for bone marrow suppression and even though not very common red cell eplasia aplastic anemia and myofibrosis have been described in patients with sle and this is as a result of bone marrow suppression um from um immune mediated destruction and then it may also be from peripheral destruction as we see in um autoimmune hemolytic anemia in the micro andropathic hemolytic anemias like robotic thrombocytopenic pepper and also with hyperexplanation penicils anemia is also seen in in sle and we know that's also immune mediated with antibodies formed against intrinsic factor and also the parietal cells impairing the absorption of b12 and anemia of chronic disorder is one of the commonest causes of anemia that you see in um sle and i'll be talking uh more in detail a bit more in detail about that the other non immune mediated causes may be as a complication of the disease or associated conditions that the patients may have like nutritional deficiencies and also because a large proportion of our patients are young females we see a lot of menorrhagia causing anemia in our patients and as previously mentioned it may be as a side effect of our treatments but for the purpose of this talk we will not go much into treatment in geocytopenia so let's let's look at anemia of chronic disorder which is a large uh which accounts for a large proportion of our anemia and sle um anemia of chronic disorder occurs in the setting of systemic um inflammation with um release of inflammatory cytokines and interleukin 6 has been noted to play a very big role in enemy of chronic disorder because it stimulates the release of hepatin from the um from the liver from the hepatocytes hep sedan um acts as a regulator of um you iron homeostasis and when we have increased levels it causes it blocks the transport of iron from the gut into the the plasma and it works very very important on the donald enterocytes also it inhibits the release of iron for macrophages in the spleen and the liver so with anemia of chronic disorder it's not so much a production problem but it's it's a disorder of the distribution of iron in the setting of the systemic inflammation it's also been um noted that in the center of systemic inflammation some cytokines like tumor necrosis factor cause bone marrow reprogramming so you will have um lymphopasses and myeloperous is going being promoted at the expense of erythropoiesis and this can cause anemia also um inflammation has been noted to cause suppression of erythropoietin and also decreases the erythropoietin receptors on the erythroid progenitor cells so you have um what looks like an erythropoietin resistance initially presents as a number 6 economic comic anemia accompanied by low transparent saturation and high or normal levels of ferritin however you it may present as some microcytic anemia and it commonly exists with iron deficiency anemia so it may be difficult to diagnose when the iron the fertility levels look almost normal and the cells look microcytic even though there is anemia of chronic disorder so that's another picture that i source for nnhgm showing anemia of chronic disorder you can see from the top left there is a an inflammation there is some inflammation going on and interleukin-6 being produced works on the liver and the hepatocytes release hepatin which works in two on in two ways where they work on the um the adrenal anterocytes where theraporting is to block the release of iron into the plasma and also on the macrophages in the spleen to block the release of iron which will inhibit um erythropoiesis because of the unavailability of iron so um we'll look briefly at some of the causes of anemia the immune related causes the first one we'll look at is autoimmune hemolytic anemia to make this diagnosis we first have to establish hemolysis and also establish that there's autoimmunity against the erythrocytes patients may present with jaundice or hematuria and then i will notice that there is an increase in the ldh of the patient because ldh is interested in iron as the erythrocytes rupture you get a release um an increase release into the bloodstream and have to global hypotoglobin will be decreased because um it binds it mops up the free um hemoglobin and that's gets used up the levels uh drop and the unconjugated um bilirubinemia indirect billion bilirubin will also be increased because um the production of um bill of the bilirubin exceeds the elimination capacity or conjugation capacity of the liver you also notice that the patient will have a reticulocytosis and because the bone marrow is now trying to compensate for this for the decreased lifespan of the erythrocytes that releases into the circulation and if you do a blood smear you see some spherocytes showing that the red blood cells are being hemolyzed to to establish autoimmunity um the the the antibodies are usually a warm type igg which are directed against the erythrocytes and if you do a composite acroms test sorry it will be positive and it may be mediated through the igg or through complements and either the igg or the c3 may be positive um pure red solid plasia and plastic anemia are rare but they have been documented there are a number of cases that have been documented in literature associated with sle and these patients will have a normochromic pneumocytic anemia which is usually severe but the other cell counts leukocytes and platelets will usually be normal the um less reticulocytopenia the severe respiratory cytopenia and if you do a bone marrow analysis you notice that there will be a lack of red cell precursors or an arrest in the differentiation of the red circuit genital cells compared to plastic anemia plastic anemia with the plastic anemia the antibodies are directed against the precursors of all the blood cell lines so in this case you have a pan cytopenia as compared to purex or the plasia where it's only the red cells that are affected so we'll move on to the white cell line uh leukopenia is defined according to the hr a american college of methodology classification criteria has a vital count of less than four which is documented on two or more occasions and this may either be as a result of lymphopenia or neutropenia nymphopena is where the absolute lymphocyte counts is less than 1.5 and the mechanism is similar to that of neutropenia and you have antibodies auto antibodies produced against the cells so you have anti-lymphocyte auto antibodies in lymphopenia and then you have anti-neutrophil antibodies in neutropenia and these antibodies promotes the lysis of the cells in lymphopenia it's also been noted that there's a decreased expression of cd55 and 59 on the surface of the lymphocytes and these are complementary regulatory proteins so the decreased expression makes the cells more susceptible to lysis by uh complements the both t and b cells are affected in lymphopenia but especially the cd4 cells are the ones that are most affected then a thrombocytopenia is also defined as a pleated count of less than 100 by the acr classification criteria and this um occurs by um immune mediated distraction so you have antibodies formed against the platelet membrane proteins we have um anti-gp2b and autobot is also again the gp3a proton on the membrane and then there are also antifreeze antibodies formed which prevents the production and maturation of the megakaryocytes and also thrombocytopenia has been noted to be seen with anti um to be associated with the presence of antiphospholipid antibodies thrombocytopenia may also occur as a result of um decreased uh production for bone marrow suppression as a result of what we mean beta distraction of the bone marrow and also from splenic sequestration of peripheral consumption let's look briefly at immune thrombus thrombocytopenia so this occurs from antibodies produced against the platelet membrane antigens and the spleen um sequestrates and and phagocytosis the um the the platelets have them as they move in the circulation patients will usually present with skin and mucous membrane bleeding and if we uh do it our investigations will usually show markedly decreased platelets uh with normal leukocyte counts and a bone marrow analysis will show increased um bone marrow megakaryocytes rarely we see abandoned syndrome um i i think i know one case that we saw in bara where we have itp or carrying together with uh coombs positive autoimmune hemolytic anemia but this is this is not very common um then ttp thrombotic number cytoplasm the pathogenesis of this is from a deficiency of metalloproteinase adams 13. um the function of which is to cleave the fundrais fundament factor and make them smaller but with the deficiency of this you will have large um multimeters of the fundamental band factor circulating in the in in circulation and this produce this predisposes to platelet aggregation and occlusive platelets by and the with all the uh plier thrombin in the circulation it causes mechanical shear stress of the red blood cells as they move in the microvasculature and the hemolyze um in the in its full-blown form you have a painter of microangiopathic melodic anemia thrombocytopenia neurological abnormalities fever and renal dysfunction but note that you may you don't need to have all these five before you suspect that the patient has um um ttp if they have microendocrine and a severe thrombocytopenia you should search for you should do a smear and search for ttp because there's a high likelihood so um just to go by the laboratory finance would be a severe thrombocytopenia and there may be associated anemia and on the blood smear you see um fragments or what we call uh schistocytes and they'll be numerous moderate to numerous sister sites will be seen and that ironic will be normal in contrast to a dic where you would have a similar picture by your eye now waist and there will be um increased urea and increase creatine and increase ldh as a result of your hemolysis and also there's you can measure the atom steady activity which will be decreased the other big disorder is antiphospholipid syndrome and three different variations have been described in sle so we have the patients with primary antiphospholipid syndrome who when followed up will eventually develop sle and we've got patients with sle who subsequently develop antiphospholipid syndrome which we tend secondary antiphospholipid syndrome and then we've also got this patient with sle with positive antiphospholipid antibodies but have never had a thrombotic event so technically they are not a full um clinical antiphospholipid syndrome so what happens is the antiphospholipid antibodies bind to the platelets and the endothelial cells and induce a pro coagulant state and also they activate complements and uh which results in tissue factor activation and this damages the endothelium endothelium and from virtual stride we know we've got damage in the endothelium we've got the pro-quad gland state so that's a a recipe for uh thrombosis antiphospholipid syndrome is it's important especially in pregnancy because the antibodies cause dysfunction of the truffle blast and also causes complement activation on the at the placenta level and this results in poor pregnancy outcome because the place the function of the placenta is impaired there's a phenomenon that i'll talk about briefly known as catastrophic antiphospholipid syndrome this is quite rare but it's a life-threatening it's also known as ashes syndrome with this you have a rapid development of multiple tumble in various organs so you have thrombi forming in different organs within a short period and it's associated with microangiopathic hibalitic anemia and zombocytopenia and this has to be picked up very early and treated because it's such a life-threatening um this slide is showing us how to make a diagnosis of antiphospholipid syndrome we use the revised sephoral classification criteria there's a clinical criteria and laboratory criteria so with the clinical criteria you need at least one episode of vascular thrombosis which may be which is non-pregnancy related and then you also need all you um or pregnancy mobility and these are quite specific what the pregnancy mobilities that are um are described are quite specific and then under the laboratory criteria you need um at least one of the antiphospholipid antibodies being positive on at least two occasions 12 weeks apart and these are your lupus anticoagulants your anticardiolithin antibody and your beta to glycoprotein one antibody so how are these um disorders that we've described um managed we will start with the cytopenias most of the cytopinea are asymptomatic so they may not need any specific treatment but you have to take note of them and investigate because they may be associated with severe illness which may be life-threatening if not picked up and treated like autoimmune hemolytic anemia like ttp or like itp also um lymphopenia has been noted to be related to disease activity so if the patient has a leukopenia or a mouth homocytopenia check to see if the patient is having a flare and if there is a flare or increased disease activity if this is managed the count should usually improve with management of the acute flare some scholars have proposed that with severe lymphopenia patients should be put on prophylactic treatment for opportunistic infections like hemostasis general basin pneumonia especially the immunosuppressive treatment but this remains controversial and we don't commonly do this and in patients with severe neutropenia which will be an absolute ritual for accounts of less than 0.5 it's recommended that if there are consequent opportunities infections or patients are at higher risk of developing a severe opportunistic infections they can be treated with granulocyte colony stimulating factors like neoproject with um so i'll go through some of the other disorders um this is based on the um american society of hematologic guidelines for management of these disorders um with associated with autoimmunity so for immune thrombocytopenia in the acute stage or first line treatment that's using glucocorticoids we can give it parentally iv or oral if the patient is stable enough to tolerate um around medication for a second line or in sub-acute uh itp which goes on for more than three months we can use as a thyroid microfinance morphetel and sometimes you can use chemotherapeutic agents like cyclophosphamide or increasing from refractory itp we can use the anti-ccd20 um biological taxoma or sometimes a splenectomy may be indicated to stop the disease process and also a new drug ramipluster has been uh identified and is in use it's a thromboprotein receptor agonist and this seems to have a good uh success with treating itp note that uh because this is related to an underlying autoimmune condition you have to control the underlying sle so that you don't get um relapses of the itp autoimmune hemolytic anemia is treated uh quite similar first line is with uh steroids and then we can use azotaprine um microphenolic morphetel um or dinosaur and then uh metaxomap is also indicated in refractory and cases and with autoimmune hemolytic anemia because there may be severe anemia you may need to support the patient with transfusion of part red cells and also remember to control the underlying sld by keeping the patient on a demand so disease-modifying agents ttp is treated the hallmark of treatment is plasmapheresis with fresh frozen plasma and we also give steroids retaximab has can be used and in refractory cases we can also give um cyclophosphamide with christian or cyclosporine there are some new drugs that have um have been studied which are showing success a recombinant form of the adam state in which is deficient in the in ttp has been um isolated and is used to treat uh ttp and also bautism which we know as one of the chemotherapeutic agents using multiple myeloma has also shown promise we need to control the underlying autoimmune disease again i can't overemphasize that and then sometimes you may need to transfuse a patient with um packed with cells if they are very anemic but a word of caution uh transfusion of platelets so you see the patient will have severe thrombocytopenia but as much as possible avoid uh transfusing these patients with platelets because it's been shown that it's really not effective and it can actually induce severe arterial thrombotic episodes and studies have shown that transfusing platelets in patients with gtp actually goes with an increase in hospital mortality so let's avoid it as much as possible unless the patient is bleeding severely and just have to do anything at all to keep patients alive anemia of chronic disorder that we've discussed um the main state of treatment is to treat the underlying condition and keep the systemic inflammation um under control pure red cell lyplasia uh first line we treat with steroids and cyclosporine a is indicated for uh perito liplesia may treat it as a thyroid as a second line treatment and in refractory cases um we can use chemotherapy cyclophosphamide and also our mtor inhibitor cereal limous can be used the new drug anti-cd52 elliptism up has also been used and has shown good success you need to transfuse these patients if they are severely anemic and in this case it's good to consider you could depleted blood for transfusion because the patient with retinal eplasia is likely to come with recurrent anemia and require recurrent transfusion and we want to prevent aluminization so for such patients it's recommended that you go gluco-depleted blood antiphospholipid syndrome is treated with long-term anticalculation we use our vitamin k antagonists and in pregnancy where there's a spontaneous we use our low molecular weight heparin so what's the implication of these uh hematological abnormalities to the sleep disease process first of all that we have to note that the timing is variable it may produce it may precede the diagnosis of sle by months or years it may occur at the time of diagnosis or care during the course of the disease so it's something to judge who's her ttp or itp unexplained with no other risk factors you have to follow up this patient because and do the autoimmune workout because there's a likelihood that they have sle that's not been diagnosed or will uh come up later also it's been noted that some of these cytopenia are this correlates with disease activity so it's it's common to see patients developing leukopenia or lymphopineal and mouth homocytopenia at the time where they are having an acute flare there are also some red zone indices that i didn't go into detail in my talk which have been noted to be um which have been noted to correlate with um an acute disease flare these are lymph your platelet lymphocyte ratio your neutrophil to lymphocyte ratio it's been noted that as this increase it's a suggestion that there's an acute flare occurring and also if your mean place that volume starts to drop or your rental distribution rate starts to increase it's a suggestion that there is an acute flare of the sle some of the cytopenia also associated with other clinical manifestations of sle and it's been shown that patients who have get homocytopenia at a greater risk of developing neuropsychiatric manifestations of sle antiphospholipid syndrome and lupus nephritis and these patients usually have a poorer disease outcome than patients who do not have a thrombocytopenia and anemia as we know is related to chronic kidney disease so we'll see that if patients with anemia should be racked up for lupus nephritis because it may be the complication of that um i'll end my talk by looking at the south african experience how what's the spectrum of hypnological abnormalities we see in our setting it's very common and and but but there's very little data that has that we have looking at the spectrum of the disorders and the associations with um sle in our population uh just a quick mention of a phenomenon called benign ethnic neutropenia that i'd like to mention now certainly it's important to note this so uh the debut classification of which opinion looks like looks at an absolute mutual account of less than 1.5 but in african populations and in some middle east population studies have shown that you can have a patient with neutrophil count of between one to 1.5 which can be completely normal and we do not need to uh over investigate and think there's actually something wrong and these patients usually have no increased risk of infection there's absence of any other abnormalities like lymphadenopathy or splenomegaly and there are no secondary causes and this is perfectly normal for um for that population in south africa there have been studies that have been done to show that we have quite uh a high percentage of people with benign ethnic neutropenia um start um in 2014 uh dr waggian prophetically did a study on patients with sle and they noticed they noted that hematological abnormalities came up as the third most common manifestation of our patients in sld after arthritis and male rash and recently i also did a study with practically about 240 240 patients at uh the baron lupus clinic and we noted that we came up with uh hematological abnormalities came up as the second most common presentation of patients at the initial diagnosis of sle anemia was the commonest um cytopenia and two thirds of the patients that initial presentation had some form of anemia and we also uh we also uh showed the association between a high um red cell distribution with with poor therapeutic outcomes and also established the association between autoimmune hemolytic anemia and the poor prognostic fee as a prognosic feature and it's association with a severe manifestation of sle in their ban patel and modi have also shown that patients who develop thrombocytopenia during the course of this of the disease as an acute presentation presents with more severe forms of the sle and is associated with the high prevalence of lupus nephritis and also associated with mortality so that's a phenomenon that we should look at pick it up and then investigate to make sure that we can treat adequately to prevent mortality the take-home message to us as general physicians and also to um methodologists that it is a common uh disorder that occurs in sle and we have to when we see a hematological disorder in a patient with smd we have to try and distinguish whether this is coming from the disease itself it's a side effect of the treatment or the patient probably has another blood dyscrasia in addition to having sle and they usually will manifest a cytopenia or calculopathy most of the time they are asymptomatic but always look out for the severe forms which need to be treated to prevent mortality like tombolic disease ttp autoimmune hemolytic anemia we also have to know that this disorders may be associated with disease activity and organ involvement and we have to investigate research and treat appropriately so um if we see a patient especially young females with unexplained hematological disorders we have to wake the patient up and do an autoimmune screen because early rheumatology referral may save the patient's life we need to treat the autoimmune the disorder and also institute treatment to control the underlying autoimmune disease to prevent relapse thank you very much for listening to my talk