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عظيم يادكتور ربنا يكرم حضرتك والله ياريت تنفعنا بحالات زي دي باستمرار ❤❤

محترم و ابن ناس و عالم جليل

ربنا يسعدك يادكتور شريف ،موفق دايماً 🩷

جزاك الله خير

Case 1, Why not thalassemia?

Case 1 1 decrease in brain perfusion by anemia 2 arterial occlusion due to it is hemolytic anemia Case 2 1Microcytic anemia ( thalassemia) 2 serum ferritin (elevated) Case 3 Immunolgical investigations to confirm autoimmune disease againaist iron receptors in Bone marrow

DIC Due to occlusion of BVs by fragmented RBCs Absent of bleeding due to anemia

1- PNHBuria or Evan's syndrome 2- sideroplastic anemia ... Iron studies and Bm examination for exclusion 3- female 45 ( ferritin , TIBC and LFTs ) -

The most likely diagnosis is Thrombotic Thrombocytopenic Purpura (TTP), characterized by the pentad of mental disturbances, fever, thrombocytopenia (platelets 105,000/cmm), microangiopathic hemolytic anemia (fragmented RBCs), and renal impairment (creatinine 1.9 mg/dL). Digital gangrene and DVT are due to widespread microvascular thrombosis and a hypercoagulable state caused by platelet aggregation. Despite thrombocytopenia, bleeding is absent as platelets are consumed in microthrombi without significant coagulation factor depletion, as indicated by normal FDP levels. The pathogenesis involves a deficiency or inhibition of the ADAMTS13 enzyme, leading to accumulation of ultra-large von Willebrand factor multimers, excessive platelet aggregation, and subsequent microvascular thrombosis.

3:51 يعطيك العافية دكتور شريف، بس أعتقد انه ال Cold agglutinin بيكون فيه ال AB هي IgM مش IgG، ممكن تكون سقطت سهواً، وتقبل مروري.❤

الحالة الأولى Hereditary spherocytosis Positive family history Increased both indirect and direct bilirubin Reticulocytosis Test needed osmotically fragility test Blood film Bone marrow biopsy

الحالة التانية Addison disease confirmed by postural syncope, hypoglycemia, areas of hyperpigmentation due to increased ACTH General weakness due to hyponatremia and hyperkalemia Tests needed Serum cortisol level at day and night CT scan of abdomen

1. ischaemic stroke most probably due SCA , B. Due vascultitis 2. Sidrobastic Anemia Peripheral blood flim 3. Bone morrow biopsies

1- Pancytopenia + normal MCV + hemolysis (reticulocytosis) + thrombosis = SLE or PNH 2- Anemia + low MCV + high serum iron + high FEP = Sideroplastic anemia confirmation of diagnosis by BM biopsy that would show RBCs with iron ring (iron in mitochondrias that are forming a ring around the nucleus) 3- I would order CBC ( to see MCV, reticulocytes count and other blood cell count) to decide what would be the next step

Q3. The only anemia in which the iron level is elevated, and if empty BM is sidroplastic anamia due to myelodysplastic syndrome. ♤ bone marrow aspiration & study for cytogenetic assessment + staining ♧ Also PBP will show = basophilic stippling. Q2 sidroplastic anamia due to Lead poisoning (result in inhibition of ferrochleate), #Pathophysiology: inhibition of aminolevulinate dehydratase and ferrochelatase → heme synthesis disruption → ↑ protoporphyrin and ↑ aminolevulinic acid in RBCs ♧ Venous blood sample for Lead level. Q1. hemolytic anemia most likely Paroxysmal nocturnal hemoglobinuria. With pancytopenia. ♧Flow cytometry of peripheral blood ♧Myelodysplastic syndrome is otherpossiblecause >>> Bone marrow aspiration biopsy.

1- Low Hb + normal MCV + reticulocytosis + positive family history = Heriditary spherocytosis Initiallly we could see spherocytes in blood smear + high MHCH in CBC test >>> Hereditary spherocytosis is diagnosed by the EMA binding test in combination with acidified glycerol lysis fragility test (EMA binding test is replaced the classic osmotic fragility test as the 'test of choice' for diagnosing hereditary spherocytosis) بتمنى من حضرتك يا دكتور تعدل الاستقصاءات دي بالنسخة الجديدة من كتبك زي ما تعودنا عليك .. بارك الله فيكم و نفع بكم 2- Female + weakness + hypoglycemia + hyperpigmentaion + postural syncope = Addison's disease (probably due to TB in develpping country & due to Autoimmune causes in develpped country) // Anemia + high MCV + pancytopenia = B12 deficieny ( may be associated with other autoimmune diseases like in this case) * To confim the diagosis of B12 deficiency we can see hypersegmented neutrophils in blood smear and measure B12 levels in blood (and B9) >> detecting Ab against pariatal cells and/or intrinsic factor. (Schilling test is not usually used) *To confirm diagnosis of Addison's disease we can measure cortislo then ACTH levels in blood >> Confirmation with cosynotrpin stimulation test .

Q1=the diagnosis is most likely is Moderate Hereditary spherocytosis with haemolytic crisis. ◇ Eosin-5-maleimide binding test is Test of choice to confirm the Diagnosis. ■ other investigations to consider are ; 1-Negative Coombs tes >>> to exclude other auto immune cause. 2-Positive osmotic fragility test >>> RBCs lysis Ratio. 3-Acidified glycerol lysis test>>> has greater sensitivity than Osmotic fragility test. 4-Blood smear >>> spherocytosis/ anisocytosis. Q2 =Diagnosis is; Autoimmune Atrophic Gastritis[AIG] (HLA B8/ HLA DR3), which is associated with pernicious anemia and primary adrenal insufficiency. ○INVESTIGATION; 1.EGD with biopsy FOR (AIG) & B12 Level + MMA + Serology. 2. Morning cortisol & ACTH + ACTH stimulation test (cosyntropin test) = for primary Addison’s

Q1..TTP or PNHuria Q2..sidroblastic anemia ..bone marrow exam Q3..Liver function test

Q1..TTP or PNHuria Q2..sidroblastic anemia ..bone marrow exam Q3..Liver function test

Q1..TTP or PNHuria Q2..sidroblastic anemia ..bone marrow exam Q3..Liver function test

brilliant, more of this clinical approaches please! BLESS YOU

1:10 Case 1 analysis ⭐️ Low hemoglobin = anemia ⭐️ Normal MCV = Normocytic ⭐️ Reticulocytosis = Stress erythropoesis ⭐️ Indirect hyperbilirubinemia (3.8) = Hemolysis ⭐️ Positive family history = Inherited hemolytic anemia ⭐️ 16 years of age, autosomal dominant inheritance pattern of disease exclude thalassemia major and intermedia ⭐️ Anemia is not mild since Hb is 9, not asymptomatic, normocytic, no anisocytosis exclude thalassemia minor ⭐️ Autosomal dominance, Spleenomegaly, no vaso-occlusive crisis even dactylitis which exclude sickle cell anemia but Combination hemoglobinopathy as Hemoglobin C / beta thalassemia would be considered 🚨 Most probable diagnosis is Hereditary spherocytosis or elliptocytosis 🚨 Investigation of choice to confirm diagnosis is “Osmotic fragility test” 1:54 Case 2 analysis ⭐️ Low hemoglobin = anemia ⭐️ High MCV = Macrocytic ➡️ Macrocytic anemia can be megaloblastic (abnormal nucleus due to Vitamin B12 or folic acid deficiency) or non-megaloblastic (abnormal cytoplasm either due to increased cell volume or incomplete cell maturation) which can be differentiate by the picture of hypersegmented neutrophils on blood smear seen in megaloblastic anemia ⭐️ Degree of anemia is moderate which is not enough to explain the frequent attacks of postural syncope ➡️ There should be another factor that explains postural hypotension ⭐️ The combination of … 1️⃣ Postural hypotension 2️⃣ Generalized weakness 3️⃣ Hypoglycemia 4️⃣ Hyperpigmentation 🚨 Suggests “Addison’s disease” -> Hypocortisolism cause hypoglycemia and elevated ACTH that cause hyperpigmentation -> Hypoaldosteronism cause postural hypotension and electrolyte imbalances “hyponatremia and hyperkalemia” causing generalized weakness 🚨 The most likely diagnosis is Auto-immune polyglandular syndrome composed of adrenal insufficiency + Pernicious anemia ✅ Investigation of choice is Upper Endoscopy and biopsy for chronic atrophic gastritis of pernicious anemia and Cortisol stress test for addison’s disease ➡️ Another possible diagnosis is Fanconi anemia which can explain hyperpigmentation, hypoglycemia and pancytopenia but i excluded it due to the patient’s age (28 years old) and the absence of other hallmark features of fanconi anemia. Genetic study and bone marrow biopsy can confirm diagnosis of fanconi anemia ➡️ Other less likely disease considered in the differentials … • Bone marrow infiltration • Liver disease (but it should cause hyperglycemia)

Second case is most probably megaloblastic anemia ( pernicious anemia) secondary to autoimmune Addison’s disease we can confirm the diagnosis by serum anti intrinsic factor antibodies and B12 level assay

Q1) 2 possibilities: Hypersplenism - PNH. Q2) Most likely diagnosis is sideroblastic anemia confirmed by bone marrow biopsy showing ringed sideroblasts. Q3) Transferrin saturation.

First case most probably HS so we can order MCHC or osmotic fragility test

The third case most probably a case of iron deficiency anemia with iron supplementation or blood transfusions So we can order TIBC and transferrin saturation

Case 1: Osmotic fragility test Case 2: Vitamin B12 deficiency complicated by pancytopenia. I will confirm my diagnosis by measuring homocysteine (which will be elevated in case of vitamin B12 deficiency and folic acid deficiency) and methylmalonic acid (which will be also elevated in case of vitamin B12 deficiency but will be normal in case of folic acid deficiency).

1- normocytic anemia with thrombosis most likely PNH the bone marrow start to fail so there is neutropenia 2- sideroblastic anemia we confirm investigation by peripheral blood smear that show basophilic stippling and bone marrow examination that shows ringed sideroblast 3-TIBC and transferrin saturation

0:31 Case 1 21 year old female with ischemic stroke and CBC presents … -> Moderate Normocytic Anemia -> Reticulocytosis -> Leukopenia -> Thrombocytopenia 🚨 Case analysis 1. Moderate Normocytic Anemia excludes defective erythropoesis which means the stages of RBC production is normal but the problem may be in the rate of production or destruction 2. Reticulocytosis means that Bone marrow is intact which excludes bone marrow failure diseases possibilities and suggests that the problem is increased rate of RBC destruction (Hemolysis) 3. Considering patient’s age, arterial thrombosis and pancytopenia … The possible etiologies of her hemolysis could be … 🚨 Possible Extra-vascular hemolysis causes; ➡️ Evans syndrome ➡️ Hypersplenism ➡️ Sickle cell disease with cerebral vasculopathy as Moymoya but it is less likely because of leukopenia (sickle cell disease presents with leukocytosis which is an important factor in pathogenesis as leukocytes shift from marginated pool to circulation as sickle cells adhere better to leukocytes) 🚨 Possible Intra-vascular hemolysis causes; ➡️ Thrombotic Microangiopathy with leukopenia can suggest certain etiologies as … ⭐️ Systemic lupus erythromatosus with anti-phospholipid syndorme ⭐️ Sepsis ⭐️ Drug-induced as chemotherapy ⭐️ Acute leukemic attack (rarely can present with leukopenia but possible) ➡️ Acute Malaria illness ➡️ Arsenic poisoning ➡️ Paroxysmal nocturnal hemoglobinuria (PNH) 0:55 Case 2 57 year old male presents with … -> Severe Microcytic Anemia -> Elevated serum iron excluded iron deficiency anemia -> Elevated free erythrocyte porphyrin indicated impaired heme synthesis 🚨 Most probable diagnoses are … 1️⃣ Chronic lead poisoning 2️⃣ Sideroblastic anemia 3️⃣ Porphyria -> Further information about patient’s clinical presentation can guide us towards the most probable diagnosis out of the three 🚨 Investigation of choice to confirm diagnosis 1️⃣ Serum and tissue lead concentration 2️⃣ Bone marrow biopsy 3️⃣ Urine porphyrin test 1:26 Case 3 45 year old female presented with -> Severe anemia -> Elevated serum iron -> Empty iron stores in bone marrow 🚨 This means increased iron concentration with decreased ferritin concentration ➡️ Therefore, iron delivery status should be evaluated -> Transferrin saturation test is needed ⭐️ High transferrin saturation suggests iron overload syndrome as in hemochromatosis or iron supplementation ⭐️ Low transferrin saturation suggests ineffective use of iron as in chronic diseases, iron-refractory anemia, … etc.

Case 1 paroxysmal nocturnal hemoglobinuria Or TTP Case 2 sideroblastic anemia or lead poisoning ??? For peripheral blood smear and bone marrow biopsy Case 3 anemia of chronic disease For s.creat, ESR

Case 1 1. Systemic Lupus Erythematosus (SLE) with Antiphospholipid Syndrome (APS): SLE can present with a stroke at a young age due to secondary APS, hematological findings (pancytopenia) due to autoimmune-mediated destruction of blood cells or bone marrow suppression. 2. Thrombotic Thrombocytopenic Purpura (TTP): For (microangiopathic hemolytic anemia, thrombocytopenia, fever, neurologic symptoms, and renal dysfunction). Case 2 The most likely diagnosis is sideroblastic anemia. For 1. Microcytic anemia & low MCV (68) 2. Elevated serum iron due to defective iron utilization. 3. Increased free erythrocyte protoporphyrin (FEP): This reflects defective heme synthesis, a hallmark of sideroblastic anemia. Case 3 The most important investigation Serum Transferrin Saturation and Total Iron-Binding Capacity (TIBC): This scenario is suggestive of a condition where iron is present but not utilized effectively, such as iron-loading anemia (e.g., sideroblastic anemia) or an iron metabolism disorder.

Case 1 heredity spherocytosis Case 2 fanconi anemia Bone marrow biopsy

Hereditary spherocytosis

Case 1 most probably autoimmune haemolytic anaemia?

ياريت الدكتور ينزل. حالة النيورو كلينيكال

جزاك الله خيرا يا دكتور ممكن ملف الشرح ؟

1-most likely SLE complicated by Acute TTP as the rise in creatinine is not specific for TTP (unlike HUS) also digital gangrene which is specific for ryanoud phenomenon which is associated with SLE Patient should do autoimmune panel eg ANA , ANCA Pt, ptt Lupus anticoagulant , anticardiolipin Coombs test 2-autoantibody directed against adamts13->decrease breakdown of vWF multimers--> vWF accumulate and lead to endothelial cell surface--> platelets adhesion and micro-thrombi formation --> fragmentation of RBCs and hemolysis with schistocytes formation Another explanation maybe be due to vasculitis related to SLE and hyper coagulation state 3-bleeding doesn’t occur until platelets count severely decreased eg less than 50.000-20.000 /cmm

ربنا يكرمك يا دكتور , بنتعلم من حضرتك دايما وحقيقي بحب حضرتك جدا 💜💜

Q1 autoimmune vasculitis most probably systemic lupus erythematosus associated with antiphospholipid syndrome for further investigations (lupus anticoagulant, anticardiolipin and anti beta 2 glycoprotein antibodies) Q2 endothelial damage, immune complex deposition, procoagulants , and arteriovenous thrombosis is characteristic for antiphospholipid syndrome Q3 1- platelets are not severly decrease > 100,000 2-Microangiopathic Hemolytic Anemia (MAHA) assosiation 3-the upper hand of the case is the hypercoagulability state Q4 mental manifestations are most probably due to the cerebral vessels vaculitis , and kidney affection duo to the immune reaction caused by systemic lupus antibodies and Antiphospholipid antibodies bind to phospholipid binding proteins on cell surfaces and This binding activates the coagulation cascade, increasing thrombus formation and promoting vascular endothelial injury and all of this with prothrombotic state, leading to increased risk of venous and arterial thrombosis.

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جزاك الله خير الجزاء استاذنا الفاضل بنستفيد كتير جدا من فديوهات حضرتك ربن يجعلها دايما فى ميزان حسنات حضرتك

Q1 Thrombotic thrombocytopenic purpura (TTP) Q2 The digital gangrene and dvt are due to micro&macro vascular thrombosis Q3 The absence of bleeding in this case is because the thrombocytopenia is primarily due to platelet aggregation into microthrombi, rather than platelet destruction or dysfunction, and the coagulation factors remain intact&(FDPs) are within normal limits in this case and if it was high would indicate a significant fibrinolysis which would cause bleeding Q4 TTP is caused by severe deficiency or inhibition of ADAMTS13, leading to excessive platelet aggregation, microvascular thrombi, and subsequent ischemia This lead to microangiopathic hemolytic anemia, thrombocytopenia, and end-organ damage

انا من العراق كيف اشترك في كورسات الدكتور؟

3:50 What is the most likely diagnosis ? ⭐️ Based on the following findings … 1) Fever 2) Hemolytic anemia “Low Hb = Anemia and Fragmented RBCs = Schistocytes = Intra-vascular hemolysis” 3) Thrombocytopenia 4) Target organ damage “CNS: altered mental status, Kidney: Elevated creatinine” 5) Evidence of Microthrombosis without coagulopathy “End organ ischemia = microthrombosis, Normal FDPs = No coagulopathy then DIC is excluded” 6) Thrombophilia evidenced by DVT, Digital gangarene, and ischemic stroke ⭐️ Since … 1) DIC is excluded by normal FDPs 2) ITP is excluded by clinical picture and Lab abnormalities “not isolated thrombocytopenia”, 3) Primary TMA is less likely due to age (it is more common in infants “congenital TTP” and children “HUS”) and clinical picture (no GIT manifestations and kidney damage is subtle as SCr is not too high “HUS is less likely” and there is evidence of hypercoagulability “Secondary TMA is more likely”) Their exclusion can be confirmed by shiga toxin and ADAMTS13 tests ⭐️ Most probable diagnosis is Secondary Thrombotic Microangiopathy ✅ Most probably secondary to Anti-phospholipid syndrome due to presence of the clinical criteria “presence of more than one episode of vascular thrombosis: the first is stroke the second is DVT and the third is Digital gangarene, should be confirmed by the laboratory criteria “LA, aCL, anti beta 2” ⭐️ Further clinical assessment and investigations to identify and confirm the secondary cause of Thrombotic Microangiopathy, for example … 1) Pregnancy test -> to exclude Gestational TMA: Pre-eclampsia/eclampsia syndrome, HELLP syndrome, Acute fatty liver of pregnancy 2) Drug history -> to exclude drug induced TMA 3) Blood pressure monitor and Fundoscopic examination -> to exclude Malignant hypertension 4) Autoimmune panel with further clinical examination especially dermatologic examination (CBC,CRP, ESR, ANA, and auto-antibodies tests) -> to exclude autoimmune diseases as anti-phospholipid syndrome, Systemic lupus erythromatosus, Scleroderma, Autoimmune vasculitis 5) Other possible causes include malignancy, HIV, post-transplantation, infection induced 4:00 Explain DVT and Digital gangrene ⭐️ They are signs of macrothrombosis indicating thrombophillic state due to Virchow’s triad (Vessel wall injury, Blood stasis, Hypercoagulability) which guides our diagnosis to secondary thrombotic microangiopathy for example… 1) Reynod’s phenomenon and vasculitis as in scleroderma, anti-phospholipid syndrome, … etc. 2) Hypercoagulation as in Malignancy, pregnancy, … etc. 4:11 Explain the absence of bleeding ⭐️Bleeding can be classified into two types according to the cause ✅ Superficial bleeding which occurs due to platelet disorder or vessel wall disorder and presents as petechiae, purpura, ecchymoses, mucosal bleeding in severe cases ✅ Deep bleeding which occurs due to coagulopathy and presents as ecchymoses, mucosal bleeding, internal bleeding as in joints, muscles, organs hematomas. -> There is no evidence of coagulopathy (DIC is excluded by normal FDPs) -> There is tendency to superficial bleeding due to prolonged bleeding time and thrombocytopenia which can be confirmed by a clinical test called Hess test … BUT why there is no petechiae presenting in the patient ?? ⭐️ Because Platelet count is not low enough to cause spontaneous petechiae and purpura (it should be more than 25% decrease from the mean predicted value, at least below 105,000) 4:21 What is the pathogenesis ? ⭐️ Anti-phospholipid syndrome Cellular apoptosis defect exposes membrane phospholipids to plasma protein binding as Beta-2 glycoprotein I. This phospholipid-plasma protein complex activates an autoimmune response leading to the production of auto-antibodies Anti-phospholipid auto-antibodies alters the homeostatic regulation of blood coagulation causing thrombosis by … 1) pro-Coagulation factors activation or anti-coagulation factors inhibition 2) Platelet activation and endothelial adherence 3) Predisposition to atherosclerosis 4) Uncontrolled Complement activation and direct cellular injury inducing thrombosis ⭐️ Thrombotic microangiopathy Auto-antibodies against ADAMTS13 decreasing its activity causing failure of vWF cleavage leading to its accumulation and Microthrombi formation causing … 1) RBCs trapping -> Intravascular hemolysis 2) Platelet consumption -> Thrombocytopenia 3) End organ hypoperfusion -> ischemia -> necrosis and inflammation which induces fever -> Target organ damage

TTP Anti phospholipid syndrome secondary to SLE Thormboctopenia TTP ( mental confusion . Hemolytic anemia with presence of many fragemented RBCS . Renal impairment . Most probably secondary to SLE . Subcide . DVT . Digital gangrane ( small vessel vasculitis ) secondary to Systemic Lupus

Question number one answer: Thrombotic thrombocytopenic purpura (TTP) Question number two answer: due to platelet aggregation forming microthrombi that occludes blood vessels and due to hypercoagulability Question number three answer: •TTP primarily affecting platelet dysfunction •Intact coagulation profile Unlike (DIC) PT and PPT are typically normal in (TTP) •Platelet count not significantly low Question number four answer: ADAMTS13 inhibition leading to excessive vWF hence platelet aggregation

1 -The diagnosis is most probably (TTP) as there is MAHA and neurological abnormalities Renal impairment 2- gangrene and DVT due to micro thrombosis 3- no bleeding as platelet count not significantly reduced (not below 50k) 4- the pathogenesis of disease is there is a deficiency in ADAM TS13 which is responsible for degradation of VWF polymers into small monomers ready for degradation

1- Anemia + schistocytes in bl smear + thrombocytopenia points towards MAHA Normal FDPs exclude DIC Fever and CNS symptoms favors the diagnosis of TTP over HUS 2- digital gangrene and DVT occurs due to hypercoaguble state Decrease level of ADAMTS13 which breakdown large multimres of vWF leads to large sticky vWF cause PLTs to clump leading to thrombus formation 3- while bleeding symptoms occur approximately in 20% of cases , in our cases PLTs number not severely reduced so there is no bleeding or petichae 4 - explained above