4.microangiopathic haemolytic anaemias (TTP, HUS)

hemolytic uremic syndrome (HUS): Tx

1. diarrhea positive HUS (typical HUS) symptomatic treatment hemodilalysis blood pressure control medications fluid management antibiotics, antimotility agents, narcotics should be avoided because they are associated with worsening of the disease NSAIDs should be avoided because they can decrease renal blood flow 2.diarrhea negative HUS (atypical HUS) plasma exchange benefits about 1/3 of children targeted therapy replacing deficient regulatory proteins in complement system factor H factor I

hemolytic uremic syndrome (HUS): Forms

1. diarrhea positive HUS (typical HUS) usually occurs after intestinal infection with Shiga-toxin producing bacteria E. coli O157:H7(shiga toxin 1 and 2) Shigella dysenteriae serotype-1 most patients are below 3 years of age (but it can also occur in adults) better prognosis 2.diarrhea negative HUS (atypical HUS) accounts for 5-10% of childhood HUS (but it can also occur in adults) associated with congenital dysfunction in the complement pathway mutation of several complement factors factor H or factor I rarely acquired due to autoantibodies against theses complement factors worse prognosis

thrombotic thrombocytopenic purpura (TTP): lab finding

1. peripheral blood smear (following two features are enough for TTP diagnosis) RCBs are so called fragmentocytes (= schistocytes) RBC membrane is damaged because big thrombi take piece of RBCs and reaming RBCs are shown as schistocytes schistocytes are morphological marker for TTP thrombocytopenia - platelets are rarely seen in blood smear 2. elevated LDH : impressively elevated

thrombotic thrombocytopenic purpura (TTP): Tx

1. plasma exchange (still essential) - so simple (but developing machine for this took long time) untreated TTP has 80-90% mortality plasma exchange can remove ULVWF multimers or autoantibodies against vWF cleaving protease FFP (fresh frozen plasma) as the replacement fluid is most widely used and cost effective do it daily at least 3-4L until platelet count reaches 150 x 109/L (150 G/L) LDH decreases schistocytes decrease 2. rituximab (anti-CD20 monoclonal antibody) also effective when there are autoantibody (IgG) against vWF cleaving protease

hemolytic uremic syndrome (HUS): clinical syptoms

1. thrombocytopenia 2. renal dysfunction 3. microangiopathic hemolytic anemia

thrombotic thrombocytopenic purpura (TTP): clinical feature

1. thrombocytopenia 2. direct Coomb's negative hemolytic anemia : profound weakness related to anemia 3. neurological abnormalities : mental status changes 4. fever : without chills 5. renal failure : proteinuria and hematouria

hemolytic uremic syndrome (HUS): prognosis

1.diarrhea positive HUS (typical HUS) usually good prognosis acute renal failure and death : 12% of cases 25% that have acute renal failure have long term renal sequelae 2.diarrhea negative HUS (atypical HUS) usually bad prognosis acute renal failure and death : 54% of cases patients need long term dialysis relapse can occur even after renal transplantation due to deficiency of complement factors

hemolytic uremic syndrome (HUS): Definition

HUS belongsof microangiopathic hemolytic anemia (MAHA) characterized by the triad symptoms (in 100% of cases) 1. hemolytic anemia 2. thrombocytopenia (MAHA) 3. renal failure

basic concepts of microangiopathic hemolytic anemia (MAHA) - a.k.a thrombotic microangiopathy (TMA)

MAHA is a microangiopathic subgroup of hemolytic anemia (category of diseases) which is caused by factors in small vessels in this category there are 4-5 important disease 1. thrombotic thrombocytopenic purpura (TTP) 2. hemolytic uremic syndrome (HUS) 3. disseminated intravascular coagulopathy (DIC) topic # 19 4. hemolysis-elevated liver enzyme-low platelet count syndrome (HELLP syndrome)

thrombotic thrombocytopenic purpura (TTP) 정의

TTP is syndrome of Coomb's negative hemolytic anemia and thrombocytopenia in the absence of an alternative explanation for theses manifestations TTP belongs to microangiopathic hemolytic anemia (MAHA)

thrombotic thrombocytopenic purpura (TTP) clinical imp. points

TTP is the most urgent medical emergency in hematology or internal medicine (still number 1) early diagnosis is the key factor for survival of the patients diagnosis on time : 95% survival diagnosis not on time : 95% death cf) 4 hematological emergency 1. TTP 2. hypercalcemia 3. spinal cord compression 4. tumorlysis syndrome

thrombotic thrombocytopenic purpura (TTP): diagnosis

classical - pentad of thrombocytopenia only 25% of patients show all these 5 symptoms (it is crazy to wait for all theses 5 symptoms for diagnosis) 1. thrombocytopenia 2. direct Coomb's negative hemolytic anemia 3. neurological abnormalities 4. fever 5. renal failure recent - 2 symptoms are enough for diagnosis can be done with peripheral blood smear 1. direct Coomb's negative hemolytic anemia 2. thrombocytopenia

thrombotic thrombocytopenic purpura (TTP) pathogenesis

deficiency of vWF-cleaving protease called ADAM-TS13 gene (to remember this name is very important in the exam) corresponding chromosome : 9q34 forms familial form of TTP - constitutional mutation in ADAM-TS13 gene acquired form of TTP - transient autoantibody such as IgG against vWF-cleaving protease mechanism (ULVWF multieric string is not cleaved) ADAM-TS13 is a gene for metalloprotease which breaks down ultra large vWF multimers (ULVWF multimer) ULVWF multieric strings secreted from Weibel-Palade bodies are anchored to the endothelial cells this passes platelets adhere via their GPIb receptors increasing platelet aggregation onto the ULVWF multimeric strings has the potential to form large occlusive platelet thrombi these strings are capable of embolizing ot microvessels downstream contributing to organ ischemia

hemolytic uremic syndrome (HUS): difference of HUS from TTP

difference of HUS from TTP 1. GI involvement 2. renal impairment (TTP also show renal impairment but it is not mandatory)

thrombotic thrombocytopenic purpura (TTP) epidermiology

epidemiology approximately 1000 new cases occur each year common in middle aged group, median age 40 female to male ratio is 2:1 onset is acute and shows fulminant course (different from ITP-idiopathic thrombocytopenic purpura) mortality rate was over 90% in pre-pheresis era relapse rate is 10-40% , ranging from months to years have been reported