Limits...
Microangiopathic Hemolytic Anemia in 57-year-old Woman with Borderline Serous Tumor of the Ovary: Real-Time Management of Common Pathways of Hemostatic Failure.

Morris GJ, Yaeger HC, Hamm F, Irwin S, Scialla SJ - Mediterr J Hematol Infect Dis (2012)

View Article: PubMed Central - PubMed

Affiliation: Mount Sinai Hospital of Queens, Long Island City, NY;

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

A 57-year-old female with history of myocardial infarction and need for cardiac catheterization with stent placement requiring clopidogrel for many years, as well as a history of hypertension requiring lisinopril, was evaluated by her gynecologist for ongoing pelvic pain... Pre-operative CA-125 level was normal, as was her complete blood count, hepatic, and renal function... Upon laparoscopy, there was found to be enlargement of the right ovary with excrescences, grossly suspicious for malignancy, thus requiring exploratory laparotomy... The differential diagnosis included microangiopathic hemolytic anemia (MAHA) associated with thrombotic thrombocytopenic purpura (TTP)/hemolytic-uremic syndrome (HUS), systemic inflammatory response syndrome (SIRS), antiphospholipid antibody syndrome, a compensated disseminated intravascular coagulation (DIC), and /or hypertension-associated MAHA... MAHA may be observed in patients who experience sepsis, disseminated carcinomatosis, disseminated intravascular coagulation, catastrophic antiphospholipid antibody syndrome (APS), organ transplantation, complications of pregnancy, malignant hypertension, and exposure to venoms, toxins, or antineoplastic agents such a mitomycin-C or cyclosporine. – Clopidogrel has previously been reported to cause TTP but usually this has been reported to occur within the first 2 weeks of initiation of the treatment., Typically the classical pentad of symptoms associated with TTP are fevers, central nervous systems changes, hemolytic anemia with shistocytes on a peripheral blood smear and associated with elevated LDH, renal insufficiency, and thrombocytopenia... Clinically, only a triad of the latter three are sufficient for a clinical diagnosis, which is curable with aggressive plasma exchange and pheresis. – Deficiency of ADAMTS13 von Willebrand factor-cleaving metalloprotease has been implicated in the pathogenesis of acute recurrent TTP, probably resulting from the combination of this deficiency due to autosomal recessive trait with decrease synthesis, intersecting with the mechanism of endothelial cell damage... Hence, when faced with these clinical signs, how does the consultant sort them out? We report another confounding trigger to the hemolytic cascade presented here... We present here a case of a 57-year-old woman previously on clopidogrel, who experienced MAHA after surgery for an ovarian mass which was deemed pathologically as a borderline serous tumor... However, post-operatively she experience fevers, renal insufficiency, hypertension, and MAHA with shistocytes and elevated LDH as well as thrombocytopenia, all suspicious for TTP, but further sorting of clinical information led to other differential diagnoses, including fever from atelectasis or SIRS, with elevated fibrinogen as in acute phase reaction; renal insufficiency from hypovolemia, as this responded to fluids; the possibility of malignant hypertension; and the possibility of DIC triggered from the release of intracellular contents from a necrotic ovarian tumor... Some common characteristics may include the activation of the coagulation system from direct contact of tumor cells with tissue factor, vis a vis, with elevated and qualitative Factor VIII, MAHA from fibrin stranding, or the presence of antiphospholipid antibodies... The difficult task is embarking on the correct and logical hematologic intervention(s), whether anticoagulation, steroids, transfusion, or aggressive plasma exchange; while life-saving in HUS/TTP, the latter may pose cardiovascular risk in some patients significant enough to consider the short-term risk versus benefit ratio... In, we summarize and propose a chronologic and strategic approach for the clinician who is faced with this dilemma of post-operative MAHA with thrombocytopenia and renal insufficiency with a large differential diagnosis including TTP, HIT, APL, and DIC. (a) Careful history must be taken with attention the onset of change in the CBC, induction of hemolysis, and consumption of platelets, concomitant with drug exposure, and put into clinical context; abrupt onset may suggest acute change, and a list of drugs may point toward more specific inciting mechanisms. (b) Physical examination with attention to hematologic manifestations such as purpura, thrombosis, and hemorrhage may help to distinguish the severity of the condition and would guide toward the absolute need for anticoagulation. (c) Immediate laboratory investigation of coagulation profile to distinguish DIC from other hemostatic disorders, including APL with the elevation of PTT alone and presence of associated antibodies, or a more normal coagulation profile in which platelet consumption may preside. (d) Visual assessment of blood cell morphology for red cell fragmentation or platelet aggregation is essential... The above described “markers” of impending hemostatic failure can help to determine which entity in the differential diagnosis to more fully pursue, and which specific intervention to follow, including plasmapheresis for TTP; anticoagulation for APL or even DIC (or its alternative for HIT); or treatment of the underlying cause with support from indicated transfusions for DIC... In this particular situation, a SIRS-like phenomenon was felt to prevail, and did not require a more intense intervention, but a successful supportive approach.

No MeSH data available.


Related in: MedlinePlus

H+E stained sections of right ovary showing borderline serous tumor. Courtesy of Dr. Sybil Irwin, Department of Pathology, Moses Taylor Hospital, Scranton, PA.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3375672&req=5

f1-mjhid-4-1-e2012030: H+E stained sections of right ovary showing borderline serous tumor. Courtesy of Dr. Sybil Irwin, Department of Pathology, Moses Taylor Hospital, Scranton, PA.

Mentions: A 57-year-old female with history of myocardial infarction and need for cardiac catheterization with stent placement requiring clopidogrel for many years, as well as a history of hypertension requiring lisinopril, was evaluated by her gynecologist for ongoing pelvic pain. She had no personal history of rheumatologic disorders, including systemic sclerosis. She had no family history of cancers. She underwent a pelvic ultrasound which showed bilateral complex ovarian cysts. She was slated for a laparoscopic bilateral salpingo-oophorectomy (BSO), and clopidogrel was stopped 2 weeks prior to surgery. Pre-operative CA-125 level was normal, as was her complete blood count, hepatic, and renal function. Upon laparoscopy, there was found to be enlargement of the right ovary with excrescences, grossly suspicious for malignancy, thus requiring exploratory laparotomy. Frozen section of the right ovary described a borderline tumor, and a hysterectomy was then performed in addition to the BSO. Estimated blood loss was 350 cc. The final pathology confirmed a serous Borderline tumor without microinvasion or evidence of invasive carcinoma in either ovary (Figure 1). Postoperatively the patient was given thromboembolism prophylaxis with heparin 5000 U subcutaneously every 8 hours. She developed fevers to 101 degrees F for 2 days without an obvious source of infection; blood and urine cultures were negative, and chest x-ray was unremarkable, with the exception of atelectasis. Empiric antibiotics however, were added. Neurologic examination was unremarkable and the patient was lucid without evidence of mental status changes. Creatinine levels rose to 2.0 mg/dL, thought due to hypovolemia, and intravenous fluids were increased. A CBC showed decrease in the platelet count to 110 K/ul (ref 142–424) on post-operative day (POD)#2, and to 63 K/ul on POD #3, when the patient was evaluated by a hematologist. The hemoglobin (Hgb) level was 8.1 g/dL (ref 12.2–16.2), prothrombin time (PT) 13.1 seconds (ref 11.7–14.7 sec), fibrinogen 550 mg/dL (ref 188–421 mg/dL), lactate dehydrogenase (LDH) 2764 U/L (ref 313–618 U/L), haptoglobin level <7 mg/dL (ref 42–312 mg/dL), and evaluation of the red cells by peripheral blood smear with 1–2 shistocytes per high-powered field (HPF) (Figure 2a). D-dimer level (fibrin-degradation split products) was 2.68 ug/ml (ref 0.0–0.42 ug/ml). Cr 1.0 mg/dL (ref <1.2 mg/dL), which was improved from 2.0 mg/dL with the addition of further IV fluids on POD#4. The patient then developed worsening blood pressure, requiring antihypertensives including clonidine, and experienced chest pain with swelling in her legs; workup including CT angiogram and an ultrasound of the lower extremities with Doppler negative for thromboembolism. Heparin was stopped and an interim diagnosis of heparin-induced thrombocytopenia (HIT) was considered; a prophylactic argatroban infusion was given while HIT studies were pending and was continued empirically for 5 days. On POD#4, platelets were 67 K/uL, Hgb 8.1 g/dL, LDH 2964 U/L, with 3–5 shistocytes per HPF (Figure 2b), with D-dimer (FDP) level 2.25 ug/ml She was neurologically intact and lucid. The patient was placed on prednisone and platelets improved to 83 K/uL on POD#5 with hemoglobin 7.7 g/dL requiring red cell transfusion, LDH 1694 U/L, fibrinogen 556 mg/dL, with liver function testing normal. HIT ELISA was negative as was heparin-induced platelet aggregation assay, and there was no evidence LAC. Factor VIII levels were followed, showing normal levels with no evidence of inhibitor, ristocetin cofactor activity was normal, and ADAMTS13 level. Creatinine level was then stable. The patient was observed on prednisone and treated empirically for fevers. On POD #6, the platelet count rose to 106 K/uL, hemoglobin to 7.9 g/dL, requiring additional red cell transfusion, LDH stable at 1610 U/L, with examination of the peripheral blood smear showing persistently 4–5 shistocytes per HPF, and creatinine level of 1.2 mg/dL. On POD#7, hgb level 9.7 g/dL, platelets 177 K/ul, LDH 1618 U/L, Cr 1.2 mg/dL, fibrinogen 301 mg/dL. On POD#8, the platelet count rose to 222 K/ul, hemoglobin to 10.2 g/dL, LDH 979 U/L, peripheral smear with 3–4 shistocytes per HPF, and stabilized for the rest of the hospitalization. The differential diagnosis included microangiopathic hemolytic anemia (MAHA) associated with thrombotic thrombocytopenic purpura (TTP)/hemolytic-uremic syndrome (HUS), systemic inflammatory response syndrome (SIRS), antiphospholipid antibody syndrome, a compensated disseminated intravascular coagulation (DIC), and /or hypertension-associated MAHA. In looking for specific trigger, we also asked the question as to whether MAHA has been triggered by ovarian tumors.


Microangiopathic Hemolytic Anemia in 57-year-old Woman with Borderline Serous Tumor of the Ovary: Real-Time Management of Common Pathways of Hemostatic Failure.

Morris GJ, Yaeger HC, Hamm F, Irwin S, Scialla SJ - Mediterr J Hematol Infect Dis (2012)

H+E stained sections of right ovary showing borderline serous tumor. Courtesy of Dr. Sybil Irwin, Department of Pathology, Moses Taylor Hospital, Scranton, PA.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3375672&req=5

f1-mjhid-4-1-e2012030: H+E stained sections of right ovary showing borderline serous tumor. Courtesy of Dr. Sybil Irwin, Department of Pathology, Moses Taylor Hospital, Scranton, PA.
Mentions: A 57-year-old female with history of myocardial infarction and need for cardiac catheterization with stent placement requiring clopidogrel for many years, as well as a history of hypertension requiring lisinopril, was evaluated by her gynecologist for ongoing pelvic pain. She had no personal history of rheumatologic disorders, including systemic sclerosis. She had no family history of cancers. She underwent a pelvic ultrasound which showed bilateral complex ovarian cysts. She was slated for a laparoscopic bilateral salpingo-oophorectomy (BSO), and clopidogrel was stopped 2 weeks prior to surgery. Pre-operative CA-125 level was normal, as was her complete blood count, hepatic, and renal function. Upon laparoscopy, there was found to be enlargement of the right ovary with excrescences, grossly suspicious for malignancy, thus requiring exploratory laparotomy. Frozen section of the right ovary described a borderline tumor, and a hysterectomy was then performed in addition to the BSO. Estimated blood loss was 350 cc. The final pathology confirmed a serous Borderline tumor without microinvasion or evidence of invasive carcinoma in either ovary (Figure 1). Postoperatively the patient was given thromboembolism prophylaxis with heparin 5000 U subcutaneously every 8 hours. She developed fevers to 101 degrees F for 2 days without an obvious source of infection; blood and urine cultures were negative, and chest x-ray was unremarkable, with the exception of atelectasis. Empiric antibiotics however, were added. Neurologic examination was unremarkable and the patient was lucid without evidence of mental status changes. Creatinine levels rose to 2.0 mg/dL, thought due to hypovolemia, and intravenous fluids were increased. A CBC showed decrease in the platelet count to 110 K/ul (ref 142–424) on post-operative day (POD)#2, and to 63 K/ul on POD #3, when the patient was evaluated by a hematologist. The hemoglobin (Hgb) level was 8.1 g/dL (ref 12.2–16.2), prothrombin time (PT) 13.1 seconds (ref 11.7–14.7 sec), fibrinogen 550 mg/dL (ref 188–421 mg/dL), lactate dehydrogenase (LDH) 2764 U/L (ref 313–618 U/L), haptoglobin level <7 mg/dL (ref 42–312 mg/dL), and evaluation of the red cells by peripheral blood smear with 1–2 shistocytes per high-powered field (HPF) (Figure 2a). D-dimer level (fibrin-degradation split products) was 2.68 ug/ml (ref 0.0–0.42 ug/ml). Cr 1.0 mg/dL (ref <1.2 mg/dL), which was improved from 2.0 mg/dL with the addition of further IV fluids on POD#4. The patient then developed worsening blood pressure, requiring antihypertensives including clonidine, and experienced chest pain with swelling in her legs; workup including CT angiogram and an ultrasound of the lower extremities with Doppler negative for thromboembolism. Heparin was stopped and an interim diagnosis of heparin-induced thrombocytopenia (HIT) was considered; a prophylactic argatroban infusion was given while HIT studies were pending and was continued empirically for 5 days. On POD#4, platelets were 67 K/uL, Hgb 8.1 g/dL, LDH 2964 U/L, with 3–5 shistocytes per HPF (Figure 2b), with D-dimer (FDP) level 2.25 ug/ml She was neurologically intact and lucid. The patient was placed on prednisone and platelets improved to 83 K/uL on POD#5 with hemoglobin 7.7 g/dL requiring red cell transfusion, LDH 1694 U/L, fibrinogen 556 mg/dL, with liver function testing normal. HIT ELISA was negative as was heparin-induced platelet aggregation assay, and there was no evidence LAC. Factor VIII levels were followed, showing normal levels with no evidence of inhibitor, ristocetin cofactor activity was normal, and ADAMTS13 level. Creatinine level was then stable. The patient was observed on prednisone and treated empirically for fevers. On POD #6, the platelet count rose to 106 K/uL, hemoglobin to 7.9 g/dL, requiring additional red cell transfusion, LDH stable at 1610 U/L, with examination of the peripheral blood smear showing persistently 4–5 shistocytes per HPF, and creatinine level of 1.2 mg/dL. On POD#7, hgb level 9.7 g/dL, platelets 177 K/ul, LDH 1618 U/L, Cr 1.2 mg/dL, fibrinogen 301 mg/dL. On POD#8, the platelet count rose to 222 K/ul, hemoglobin to 10.2 g/dL, LDH 979 U/L, peripheral smear with 3–4 shistocytes per HPF, and stabilized for the rest of the hospitalization. The differential diagnosis included microangiopathic hemolytic anemia (MAHA) associated with thrombotic thrombocytopenic purpura (TTP)/hemolytic-uremic syndrome (HUS), systemic inflammatory response syndrome (SIRS), antiphospholipid antibody syndrome, a compensated disseminated intravascular coagulation (DIC), and /or hypertension-associated MAHA. In looking for specific trigger, we also asked the question as to whether MAHA has been triggered by ovarian tumors.

View Article: PubMed Central - PubMed

Affiliation: Mount Sinai Hospital of Queens, Long Island City, NY;

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

A 57-year-old female with history of myocardial infarction and need for cardiac catheterization with stent placement requiring clopidogrel for many years, as well as a history of hypertension requiring lisinopril, was evaluated by her gynecologist for ongoing pelvic pain... Pre-operative CA-125 level was normal, as was her complete blood count, hepatic, and renal function... Upon laparoscopy, there was found to be enlargement of the right ovary with excrescences, grossly suspicious for malignancy, thus requiring exploratory laparotomy... The differential diagnosis included microangiopathic hemolytic anemia (MAHA) associated with thrombotic thrombocytopenic purpura (TTP)/hemolytic-uremic syndrome (HUS), systemic inflammatory response syndrome (SIRS), antiphospholipid antibody syndrome, a compensated disseminated intravascular coagulation (DIC), and /or hypertension-associated MAHA... MAHA may be observed in patients who experience sepsis, disseminated carcinomatosis, disseminated intravascular coagulation, catastrophic antiphospholipid antibody syndrome (APS), organ transplantation, complications of pregnancy, malignant hypertension, and exposure to venoms, toxins, or antineoplastic agents such a mitomycin-C or cyclosporine. – Clopidogrel has previously been reported to cause TTP but usually this has been reported to occur within the first 2 weeks of initiation of the treatment., Typically the classical pentad of symptoms associated with TTP are fevers, central nervous systems changes, hemolytic anemia with shistocytes on a peripheral blood smear and associated with elevated LDH, renal insufficiency, and thrombocytopenia... Clinically, only a triad of the latter three are sufficient for a clinical diagnosis, which is curable with aggressive plasma exchange and pheresis. – Deficiency of ADAMTS13 von Willebrand factor-cleaving metalloprotease has been implicated in the pathogenesis of acute recurrent TTP, probably resulting from the combination of this deficiency due to autosomal recessive trait with decrease synthesis, intersecting with the mechanism of endothelial cell damage... Hence, when faced with these clinical signs, how does the consultant sort them out? We report another confounding trigger to the hemolytic cascade presented here... We present here a case of a 57-year-old woman previously on clopidogrel, who experienced MAHA after surgery for an ovarian mass which was deemed pathologically as a borderline serous tumor... However, post-operatively she experience fevers, renal insufficiency, hypertension, and MAHA with shistocytes and elevated LDH as well as thrombocytopenia, all suspicious for TTP, but further sorting of clinical information led to other differential diagnoses, including fever from atelectasis or SIRS, with elevated fibrinogen as in acute phase reaction; renal insufficiency from hypovolemia, as this responded to fluids; the possibility of malignant hypertension; and the possibility of DIC triggered from the release of intracellular contents from a necrotic ovarian tumor... Some common characteristics may include the activation of the coagulation system from direct contact of tumor cells with tissue factor, vis a vis, with elevated and qualitative Factor VIII, MAHA from fibrin stranding, or the presence of antiphospholipid antibodies... The difficult task is embarking on the correct and logical hematologic intervention(s), whether anticoagulation, steroids, transfusion, or aggressive plasma exchange; while life-saving in HUS/TTP, the latter may pose cardiovascular risk in some patients significant enough to consider the short-term risk versus benefit ratio... In, we summarize and propose a chronologic and strategic approach for the clinician who is faced with this dilemma of post-operative MAHA with thrombocytopenia and renal insufficiency with a large differential diagnosis including TTP, HIT, APL, and DIC. (a) Careful history must be taken with attention the onset of change in the CBC, induction of hemolysis, and consumption of platelets, concomitant with drug exposure, and put into clinical context; abrupt onset may suggest acute change, and a list of drugs may point toward more specific inciting mechanisms. (b) Physical examination with attention to hematologic manifestations such as purpura, thrombosis, and hemorrhage may help to distinguish the severity of the condition and would guide toward the absolute need for anticoagulation. (c) Immediate laboratory investigation of coagulation profile to distinguish DIC from other hemostatic disorders, including APL with the elevation of PTT alone and presence of associated antibodies, or a more normal coagulation profile in which platelet consumption may preside. (d) Visual assessment of blood cell morphology for red cell fragmentation or platelet aggregation is essential... The above described “markers” of impending hemostatic failure can help to determine which entity in the differential diagnosis to more fully pursue, and which specific intervention to follow, including plasmapheresis for TTP; anticoagulation for APL or even DIC (or its alternative for HIT); or treatment of the underlying cause with support from indicated transfusions for DIC... In this particular situation, a SIRS-like phenomenon was felt to prevail, and did not require a more intense intervention, but a successful supportive approach.

No MeSH data available.


Related in: MedlinePlus