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ICU Care of Thrombocytopenia
《1》 pathophysiological classification of thrombocytopenic states
I. increased platelet destruction
A. immune thrombocytopenias
1. idiopathic: ITP
2. secondary: infection induced, drugs induced, posttransfusion purpura,
autoimmune hemolytic anemia (Evans syndrome), SLE,
hyperthyroidism, lymphoproliferative disorders, allergy, anaphylaxis
3. neonatal immune thrombocytopenias
B. nonimmune thrombocytopenias
1. due to platelet consumption: microangiopathic hemolytic anemia,
DIC, chronic relaspsing schistocytic hemolytic anemia, hemolytic
uremic syndrome, thrombotic thrombocytopenia purpura,
Kasabach-Merritt syndrome, cyanotic heart disease
2. due to platelet destruction: drugs( ristocetin, protamine sulfate,
bleomycin), left ventricular outflow obstruction, infections, cardiac,
malignant hypertension
II. disorders of platelet distribution or pooling
A. hypersplenism: portal hypertension, Gaucher disease, cyanotic heart
disease, neoplastic, infection
B. hypothermia
III. decreased platelet production-deficient thrombopoiesis
A. hypoplasia or suppression of megakaryocytes: drugs, constitutional
(thrombocytopenia absent radii-TAR syndrome, congenital,
megakaryocytic hypoplasia without anomalies, congenital hypoplastic
thrombocytopenia with microcephaly, Rubella syndrome, Trisomy 13, 18,
Fanconi’s anemia), ineffective thrombopoiesis (severe IDA, certain
familial thrombocytopenias, paroxysmal nocturnal hemoglobinuira),…
B. marrow infiltrative processes:
1. benign: osteopetrosis, storage diseases
2. malignant: De novo( leukemias, myelofibrosis, Langerhans cell
histocytosis, histiocytic medullary reticulosis), secondary
(lymphomas, neuroblastoma, other solid tumor metastasis)
《2》 heparin induced thrombocytopenia
I. definition: IV or SC heparin -> progressive thrombocytopenia during the first 10
days and prompt recovery when heparin is discontinued
II. etiology: direct interaction of heparin with platelets; heparin-dependent
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antiplatelet antibody (an IgG antibody specific for complexes of heparin and
the heparin-binding cationic protein, platelet factor 4)..
III. clinical features:
1. minimal thrombocytopenia: platelet >50,000/µl, begin soon after heparin
treatment; most common; caused by the direct agglutinating effect of heparin
on platelets; heparin-dependent antiplatelet antibody may negative
2. severe thrombocytopenia: less common; 5 to8 days later of heparin therapy;
may be accompanied by thrombosis or DIC; associated with
heparin-dependent antiplatelet antibody; bleeding is rarely an issue; major
clinical problem is thrombosis
IV. laboratory features:
1. functional assays: based on end points of platelet aggregation or secretion
2. antigen assays: based on ELISA using heparin-PF4 as the target antigen
V. prevention, diagnosis and therapy:
1. awareness of the potential for the thrombocytopenia with heparin use
2. frequency performance of platelet counts
3. diagnosis: platelet drop less than 10,000/µl; platelet count decrease by
greater than 50% that is not explained by other cause; a new
thromboembolic event in the absence of other etiologies
4. if the platelet drop to 50,000/µl or any evidence of thrombosis, heparin
should be discontinued
5. evidence of DIC should be assessed, which may itself be caused by the
heparin; all heparin-associated platelet and coagulation changes should be
reverse within several days of stopping heparin
6. most patient: thrombocytopenia will be mild and self limited and will be
discovered at a time in the course of therapy when heparin can be safely
discontinued
7. treatment for severe thrombocytopenia with thrombosis may include the use
of plasma exchange
《3》 platelet transfusion
I. factors affecting the decision to infusion platelets:
1. degree of thrombocytopenia,
2. duration of thrombocytopenia,
3. mechanism of thrombocytopenia,
4. associated bleeding tendencies
II. Guidelines for Pediatric Platelet Transfusions
Children and Adolescents
PLTs <50,000/µl and bleeding; PLTs <50,000/µl and invasive procedure
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PLTs <20,000/µl & marrow failure with additional hemorrhagic risk factors
Infants Within First 4 Mo of Life
PLTs <100,000/µl & bleeding; PLTs <50,000/µl & invasive procedure
PLTs <20,000/µl & clinically stable; PLTs <100,000/µl & clinically unstable
III. Therapy:
1. ideal PLT transfusions: to raise the PLT count to >50,000/µl, and for
neonates to >100,000/µl, this can be achieved consistently by the infusion
of 10 ml/kg of standard platelet concentrates
2. PLT concentrates should be transfused as rapidly as the patient's overall
condition permits, certainly within 2 hr
3. It is important to minimize transfusion of Group O PLTs to group A or B
recipients, as passive anti-A or -B can lead to hemolysis
4. refractory platelet transfusion: one-hour post platelet transfusion
increment in a platelet count of less than 20,000/µl-> single-donor
platelet should be matched (HLA typing, platelet specific, ABO antigens)
5. if refractory to matched platelet transfusion-> bleeding occur: very large
amount of platelet may overcome the antibody-mediated destruction, or
IVIG given before platelet transfusion may improve the transfusion
response
References:
1. Willians Hemotology 6th edition (1995)
2. Nathan and Oski’s Hemotology of Infancy and Childhood 5th edition (1998)
3. Manual of Pediatric Hemotology and Oncology 3rd edition (2000)
黃芳亮醫師編寫 張德高主任審定
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Tumor Lysis Syndrome
《1》 etiology and pathophysiology
I. metabolic abnormalities result from the death of tumor cells and release of
their contents into the circulation;
1. clinic triad : hyperuricemia, hyperphosphatemia and hyperkalemia;
2. symptomatic hypocalcemia can develop secondary to formation of calcium
phosphate from the hyperphosphatemia;
3. usually appear 12 to 72 hours from the initiation of therapy
II. occurs most common in malignant lymphoma, ALL particular T-cell linage
ALL with hyperleukocytosis and extensive extramedullary disease, also noted
in neuroblastoma, medulloblastoma, rare in AML and CML
1. potassium: rapid rise in potassium can cause cardiac arrest
2. uric acid comes from the breakdown of the released nucleic acids
3. lymphoblasts are rich in phosphate , elevated levels of serum phosphate
are exacerbated by a metabolic acidosis, when the solubility product
factor (Ca x P) reaches 60, calcium phosphate precipitates in the
microvasculature, causing a secondary hypocalcemia
4. acute renal failure
《2》 evaluation and differential diagnosis
I. onset of symptoms referable to the malignancy: abdominal pain or fullness,
back pain, vomiting, diarrhea, dehydration, anorexia, cramps, spasms, tetany,
seizure, alternations in consciousness
II. examination including: blood pressure, cardiac rate, rhythm, abdominal
masses, presence of pleural effusion or ascites, signs of SVCS or SMS and
signs of cerebral anoxia
III. studies: CBC, determination of serum sodium, potassium, chloride,
bicarbonate, calcium, phosphorus, uric acid, BUN, Cr, urinalysis, albumin;
EKG if the serum potassium is high; abdomen sono or CT scan; chest x-ray
for mediastinal mass
《3》 therapy
I. general management:
1. strictly monitor urine output, specific gravity, and pH
2. monitor electrolytes, uric acid, calcium, creatinine at least every 6 hours
3. provide cardiac monitoring if hyperkalemia or hypocalcemia
4. respiratory and CNS monitoring
5. leukapheresis or exchange transfusion: can be used if initial white cell
count is greater than 100,000/mm3 and prevention PRBC transfusion
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II. hydration: most critical factor in treatment of tumor lysis syndrome;
increased urinary outflow, improved glomerular filtration rate, maintenance
fluid volume 2x to 4x as 5% G/S 1/4 NS with 40-80 mEq of sodium
bicarbonate per liter; no potassium; urine output should be maintained at
more than 100 ml per M2 per hour with a specific gravity of no more than
1.010
III. alkalization: keep urine pH 7.0 to 7.5; increased NaHCO3 as needed; stop
NaHCO3 if serum bicarbonate level reaches 30 mEq/L or the urine pH> 7.5
IV. uric acid reduction: allopurinol 250-500 mg/M2/day to a maximum of 800
mg (initial 100 mg/M2/dose Q8H); prevents uric acid synthesis; helps
prevent urate nephropathy
V. management hyperkalemia by these measures:
1. do not administer any intravenous potassium
2. provide hydration and alkalization
3. administer sodium polystyrene sulfonate (Kayexalate – an ion
exchange resin) in a dose of 1 g/kg/dose q6h orally or via nasogastric
tube with sorbitol 50-150 ml (the practical exchange ratio is 1 mEq of
potassium / L / g resin over 24 hours)
4. if serum K+ concentration increase to 7 mEq/L or more, use the
following: insulin 0.1 units/kg/h with glucose 0.5g/kg/h as a
continuous infusion or hemodialysis
VI. management hyperphosphatemia and hypocalcemia as follow:
1. correct serum phosphate through hydration, alkalinization
2. avoid calcium administration (as the product of serum calcium and
serum phosphorus approaches 60, metastatic calcification can occur
and exacerbate renal damage)
VII. dialysis: to be used for progressive renal failure with potassium > 6 mEq/L,
phosphate >10 mg/dl, oligouria, anuria, and volume overload unresponsive
to the mannitol or lasix ( mannitol : 0.5-1 g/kg; lasix 0.5-1.0 mg/kg: can be
used if patient has oliguria unresponsive to increased hydration); volume
overload: pleural pericardia effusion; hyperuricemia; symptomatic
hypocalcemia.
References:
1. Willians Hemotology 6th edition (1995)
2. Nathan and Oski’s Hemotology of Infancy and Childhood 5th edition (1998)
3. Manual of Pediatric Hemotology and Oncology 3rd edition (2000)
黃芳亮醫師編寫 張德高主任審定
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