H/O Flashcards
Thrombotic thrombocytopenic purpura
a clinical diagnosis that requires the presence of thrombocytopenia and microangiopathic hemolytic anemia, which is confirmed by schistocytes on the peripheral blood smear. Patients may also have fever; kidney manifestations such as hematuria, elevated creatinine level, and proteinuria; and fluctuating neurologic manifestations, but the absence of these symptoms does not exclude the diagnosis. Assays for ADAMTS-13 activity and inhibitor titer are available but are best used for prognosis rather than to guide therapy, because TTP requires immediate treatment with plasma exchange that cannot be delayed until laboratory test results are available.
Major bleeding associated with vitamin K antagonists
Should be treated by reversing anticoagulation with 4-factor prothrombin complex concentrate in addition to intravenous vitamin K.
4-factor prothrombin complex concentrate
Contains all four vitamin K–dependent coagulation factors (factors II, VII, IX, and X) Unlike fresh frozen plasma (FFP), 4f-PCC is stored at room temperature, does not require ABO typing, and can be infused quickly because of its small volume, thus reducing the time to delivery of therapy. Compared with FFP, 4f-PCC has been shown to more rapidly achieve hemostasis in patients with visible or musculoskeletal bleeding with less risk of fluid overload and no difference in thromboembolic events. This agent has therefore been approved by the FDA for urgent reversal of coagulation factor deficiencies related to vitamin K antagonist therapy for adult patients with acute major bleeding, as well as for adult patients in need of urgent surgery or an invasive procedure.
chronic thromboembolic pulmonary hypertension (CTEPH)
efined as a mean pulmonary artery pressure of greater than 25 mm Hg, with normal pulmonary capillary wedge pressure, left atrial pressure, and left ventricular end-diastolic pressure. It typically occurs within 2 years following a pulmonary embolism (PE), affecting 3.8% of patients, although only about 50% of these have a history of clinically detected PE If the V/Q scan suggests CTEPH, confirmatory right heart catheterization with pulmonary artery pressure measurements and pulmonary arteriography is indicated.
paroxysmal nocturnal hemoglobinuria (PNH)
Hemolytic anemia, pancytopenia, or unprovoked atypical thrombosis. Hemolysis is caused by the absence of decay-accelerating factor (CD55) and the membrane inhibitor of reactive lysis (CD59), which are glycosylphosphatidylinositol-dependent complement regulatory proteins Mutations in the PIG-A gene lead to the reduction or absence of glycosylphosphatidylinositol, an important erythrocyte-anchoring protein
Budd-Chiari syndrome associated with
Half of patients with idiopathic BCS had an acquired mutation in JAK2, without overt suggestion of a myeloproliferative neoplasm. Therefore, testing for JAK2 is part of the diagnostic testing protocol that includes consideration of paroxysmal nocturnal hemoglobinuria in the differential diagnosis of splanchnic vein thrombosis.
Hemophilia
Hemophilia A results from factor VIII deficiency and hemophilia B from factor IX deficiency; both produce a prolongation of the activated partial thromboplastin time that fully corrects in a mixing study.
hypereosinophilic syndrome (HES)
An elevated eosinophil count (>1500/µL [1.5 × 109/L]) without a secondary cause and evidence of organ involvement are diagnostic. Causes of eosinophilia are described in the CHINA: connective tissue diseases, helminthic infection, idiopathic [HES], neoplasia, allergy
Urticaria pigmentosa
Pruritic yellow to red or brown macules, papules, plaques, and nodules. Systemic mastocytosis with eosinophilia is characterized by urticaria pigmentosa. The most common noncutaneous findings are gastrointestinal and include symptoms such as abdominal pain, diarrhea, nausea, and vomiting.
identification of an inherited thrombophilia
Often does not change treatment decisions in a patient with VTE (does not reliably predict risk of recurrence or influence duration of recommended anticoagulation), evidence-based guidelines recommend against routine thrombophilia testing. In patients with an unprovoked proximal DVT, the recommendation for long-term anticoagulation would not be altered by the results of such testing, thus, it would not be helpful. Testing may be indicated, however, in patients with VTE at intermediate risk for recurrence by traditional predictors in whom finding a strong thrombophilic risk might alter therapeutic decisions.
transfusing select patients who are immunocompromised to reduce the risk of transfusion-associated graft-versus-host disease and febrile nonhemolytic transfusion reaction.
Leukoreduced and irradiated erythrocytes should be used (those with severe, inherited T-cell immunodeficiency syndromes or Hodgkin lymphoma or recipients of allogeneic or autologous hematopoietic stem cell transplantation, purine analog–based chemotherapy [fludarabine, cladribine, deoxycoformycin], alemtuzumab, or rabbit antithymocyte globulin therapy) are at increased risk of developing transfusion-associated graft-versus-host disease (ta-GVHD)
Washed erythrocytes
considered for patients with a history of severe allergic reactions to transfusions patients who are IgA deficient
acute lymphoblastic leukemia (ALL) in older patients
Diagnosis: presence of 25% or more lymphoblasts on bone marrow examination. Cytochemical stains and flow cytometry can help distinguish ALL from acute myeloid leukemia (AML) and B-cell from T-cell ALL prognosis for an older patient with ALL has traditionally been poor, with Philadelphia chromosome [t(9;22)] positivity indicating worse outcomes The most significant advance in the treatment of older patients with Philadelphia chromosome–positive disease is TKI therapy. The results of dasatinib and dexamethasone therapy are better than those for traditional chemotherapy, with less toxicity. For older patients who have Philadelphia chromosome–negative ALL, no clear standard cytotoxic chemotherapy regimen exists. However, TKI therapy can provide disease control for greater than 1 year with much less toxicity. Combination regimens such as hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD) can cure adults with ALL, but are too toxic for use in elderly populations. The paradox of ALL in older adults is that although less aggressive regimens are less toxic, they compromise the ability to control the leukemia.
HLA-matched platelets.
Patients experiencing platelet transfusion refractoriness because of alloimmunization should receive
β-thalassemia
Hemolytic anemia, microcytosis, and target cells are typical of β-thalassemia, which is associated with slightly increased hemoglobin A2 and some residual hemoglobin F.
elevated erythropoietin level and hypoxemia
secondary erythrocytosis. Don’t need bone marrow biopsy.
acquired hemophilia
associated with high titers of inhibitor. Recombinant activated factor VII is used to treat the bleeding episodes. Patients with low titers of inhibitor (measured in Bethesda units) may be treated with factor VIII concentrates. Patients with high inhibitor titers (>5 Bethesda units) require treatment with recombinant factor VIIa or prothrombin complex concentrates designed to activate factor X and secure hemostasis independent of factor VIII and the intrinsic pathway. Patients may require immunosuppression for inhibitor eradication.
In some patients with fluctuating INRs while taking warfarin
daily supplementation with low-dose vitamin K (100-150 µg/d) can stabilize the INR.
parvovirus and sickle cell disease
Parvovirus B19 infection can cause acquired pure red cell aplasia in an otherwise functionally asplenic patient with sickle cell disease.
immune thrombocytopenic purpura treatment
without evidence of bleeding and platelet counts greater than 30,000 to 40,000/µL (30-40 × 109/L) have less than a 15% chance of developing more severe thrombocytopenia requiring treatment and can be managed with careful observation. Repeat the complete blood count at a designated interval, generally 1 to 2 weeks, u ITP is a diagnosis of exclusion, supportive clinical findings include an otherwise normal blood count and the absence of additional organ dysfunction. Platelets on the peripheral blood smear are large because they typically have been recently released from the marrow, and the enhanced hemostatic function of these young platelets may account for less severe bleeding symptoms than those associated with other diseases with a similar platelet count. therapy may be required for patients with platelet counts lower than 30,000 to 40,000/µL (30-40 × 109/L) or with bleeding. Initial therapy consists of glucocorticoids. Patients who do not respond to glucocorticoid therapy should be treated with an additional agent such as intravenous immune globulin or anti-D immune globulin or rituximab. Splenectomy leads to a sustained remission in 75% of patients.
Isolated superficial venous thrombophlebitis
Duplex ultrasonography is indicated to assess for the possibility of an associated deep venous thrombosis (DVT) in patients with isolated superficial venous thrombophlebitis (SVT), because DVT or pulmonary embolism risk increases in patients with SVT of the great or small saphenous vein, with extremity swelling more pronounced than would be expected from the SVT alone, and with progressive symptoms. Nonextensive SVT, defined as less than 5 cm in length and not near the deep venous system, may be treated with only symptomatic therapy consisting of analgesics, anti-inflammatory medications, and warm or cold compresses for symptom relief, because the risk of progression into the deep venous system and of PE is low.
folate deficiency
Those with generalized malnutrition or poor nutrition, can become folate deficient in weeks to months because of relatively limited stores of folate in the body. Measuring serum folate levels is typically unreliable in diagnosing folate deficiency, because folate levels increase rapidly after a single folate-containing meal. Plasma homocysteine levels increase in folate deficiency, whereas homocysteine and methylmalonic acid levels are increased in cobalamin deficiency.
Treatment of essential thrombocythemia
Hydroxyurea plus low-dose aspirin is the best treatment option for essential thrombocythemia when treatment is required in patients older than 60 years, those with a platelet count greater than 1 million/µL (1000 × 109/L), or those with a history of thrombosis.
Heyde’s syndrome
a syndrome of gastrointestinal bleeding from angiodysplasia in the presence of aortic stenosis Caused by the induction of Von Willebrand disease type IIA (vWD-2A) by a depletion of Von Willebrand factor (vWF) in blood flowing through the narrowed valvular stenosis. Can also get a MAHA from valvular replacement/disease.
Associated with ingestion of raw seafood, especially oysters, and the risk of sepsis and death is increased in persons with hereditary hemochromatosis.
Vibrio vulnificus
iron overload syndromes
excess iron appears to impair host defenses against certain infections, such as decreasing the chemotactic response and compromising the ability of phagocytic cells. The result is increased virulence among specific infectious organisms in patients with iron overload, including Vibrio species (vulnificus,cholerae), Escherichia coli, Yersinia enterocolitica, Listeria monocytogenes, cytomegalovirus, hepatitis B and C viruses, and HIV. Fungi include Aspergillus fumigatus and mucor.
factor V Leiden (FVL) mutation
Homozygous FVL carries an 18-fold increased risk of first-time venous thromboembolism (VTE), whereas FVL heterozygosity only carries a 2.7-fold increased risk. no evidence indicates testing for inherited thrombophilia is beneficial in an asymptomatic child, particularly with heterozygous FVL, which is not considered a strong thrombophilia. In patients in whom testing for FVL is indicated, the presence of FVL can be detected by an APC resistance assay that assesses the ability of protein C to inactivate factor Va. This is a very sensitive study that effectively excludes FVL if normal and is the preferred initial screening test, mainly because it is typically less expensive than the FVL genetic test.
acute promyelocytic leukemia
All-trans retinoic acid (ATRA) should be administered as soon as possible, followed by chemotherapy, for this patient with acute promyelocytic leukemia APL is a clinically and biologically distinct variant of acute myelocytic leukemia characterized by the presence of a (15;17) gene translocation, which gives rise to the promyelocytic leukemia–retinoic acid receptor-α fusion transcript and arrest of leukemic cells at the promyelocyte stage. ATRA to standard induction and consolidation chemotherapy releases the block in promyelocyte maturation and produces cure in up to 80% of patients.
hereditary spherocytosis
The osmotic fragility test with 24-hour incubation is a key step in diagnosing hereditary spherocytosis. Autosomal dominant
sickle cell disease, including pregnant patients, transfusion
not indicated for uncomplicated pregnancy, routine painful episodes, minor surgery not requiring anesthesia, or asymptomatic anemia. Erythrocyte exchange transfusion is indicated for acute ischemic stroke, ACS with significant hypoxia, and multiorgan failure/hepatopathy as well as in persons in whom simple transfusion would increase the hemoglobin level to greater than 10 g/dL (100 g/L). Chronic transfusion can lead to iron overload, alloimmunization, and an increased risk for a delayed hemolytic transfusion reaction. Erythrocytes used in transfusion should be leukoreduced, hemoglobin S negative, and phenotypically matched for the E, C, and K antigens as well as for any known alloantibodies. Hemoglobin targets should remain less than 10 g/dL (100 g/L) to avoid hyperviscosity.
In patients taking a vitamin K antagonist who have an INR greater than
9 and no evidence of bleeding, oral vitamin K and withholding warfarin are indicated to rapidly reduce the INR. For a supratherapeutic INR less than 5.0, withholding warfarin and restarting at a lower dose are usually adequate. For an INR of 5.0 to 9.0, a similar management strategy is appropriate, although administration of 1 to 2.5 mg of oral vitamin K is reasonable in patients at risk for bleeding. In patients with an INR greater than 9.0, such as this patient, administration of 2.5 to 5 mg of oral vitamin K is indicated to more rapidly reduce the INR to the desired range.
smoldering (asymptomatic) multiple myeloma
M protein level of 3 g/dL or more or clonal plasma cells representing 10% or more of the total marrow cellularity on bone marrow biopsy but the absence of disease-specific signs or symptoms median time to progression of 4.8 years. Therefore, surveillance in these patients is necessary
von Willebrand disease
easy bruising, postsurgical bleeding, and heavy menstrual bleeding in women in conjunction with normal prothrombin and normal to minimally prolonged activated partial thromboplastin times.
heparin-induced thrombocytopenia.
The 4T score is used to estimate the pretest probability of HIT based on clinical factors, including degree of thrombocytopenia, timing of the decrease in platelet count, presence of any potential sequelae of HIT (such as thrombosis), and whether another potential cause for thrombocytopenia exists. Possible point values range from 0 to 8; scores of 0 to 3 indicate low probability, 4 or 5 indicate intermediate probability, and 6 to 8 represent high pretest probability. Confirmatory testing for antiplatelet antibodies may be done by direct antibody testing or by functional assays that test the ability of serum from patients with HIT to activate test platelets. Direct antibody testing is typically performed by enzyme-linked immunosorbent assay (ELISA) that detects antibodies directed toward heparin-platelet factor 4 complexes. The two commonly used functional assays are the serotonin release assay (SRA) and the heparin-induced platelet aggregation (HIPA) assay.
polycythemia vera
Symptoms include generalized pruritus that often worsens after bathing, erythromelalgia (a burning sensation in the palms and soles), and hypermetabolic symptoms such as fever, weight loss, and sweating. On physical examination, patients may have plethora and hepatosplenomegaly. Twenty percent of patients experience arterial or venous thrombosis as their initial symptom. PV and the other MPNs predispose to the development of the Budd-Chiari syndrome (BCS), which is characterized by hepatic venous outflow tract obstruction (including the suprahepatic inferior vena cava) and other intra-abdominal thromboses, such as thrombosis of the portal, superior mesenteric, or splenic vein. Anticoagulant therapy is recommended for all patients with BCS regardless of whether an underlying prothrombotic disorder is discovered. Phlebotomy to normalize the hematocrit (goal <45% in men, <42% in women) is indicated, and adding the myelosuppressive agent hydroxyurea to phlebotomy decreases thrombotic events in patients with PV.
Diagnose cold agglutinin disease
A direct antiglobulin (Coombs) test is the most appropriate diagnostic step. Direct IgM binds more effectively at temperatures colder than 32.0 °C (89.6 °F), typically in the fingers, toes, and nose, causing cold agglutinin disease. IgM-coated erythrocytes agglutinate in the microvasculature, leading to cyanosis and ischemia in the cold extremities. The IgM antibodies fix complement and then detach from erythrocytes when they return to the warmer body core. An acquired hemolytic anemia associated with cold exposure and supported by his peripheral blood smear, showing agglutinated erythrocytes that disappear when warmed. Cold agglutinin disease may occur as a primary disorder or may be associated with a lymphoproliferative disorder or certain infections, such as Mycoplasma pneumoniae or Epstein-Barr virus. The primary treatment for cold agglutinin disease is avoidance of cold exposure.
clotting factor activity levels in liver failure, disseminated intravascular coagulation, or vitamin K deficiency/warfarin overdose
In liver failure, all clotting factor activity levels are low except for factor VIII, which is synthesized in all endothelial cells rather than only hepatic endothelial cells
Additionally, good hepatic function is required for factor VIII clearance, thus factor VIII levels increase in liver disease. Patients with severe liver failure (and on occasion those with acute liver failure) will have prolonged prothrombin and activated partial thromboplastin times because of decreased levels of coagulation factors. This is called the coagulopathy of liver disease. The elevated D-dimer level is also consistent with liver disease, because D-dimers are cleared by the liver; a high D-dimer level does not automatically indicate disseminated intravascular coagulation (DIC).
An elevated factor VIII level, as seen in this patient, rules out DIC.
Factor V levels can be used to distinguish between liver disease and vitamin K deficiency, because factor V is synthesized in the liver but is not a vitamin K–dependent factor. Thus, someone with vitamin K deficiency will have normal levels of factor V, whereas a patient with liver failure will have low factor V levels.
IGH/CD1
mantle cell lymphoma
PML-RAR
cute promyelocytic leukemia
chronic myeloid leukemia
insidious onset of fatigue; early satiety and progressive weight loss associated with splenomegaly; and a peripheral blood smear demonstrating myelocytes, metamyelocytes, and basophils. The peripheral blood smear of CML is commonly described as mimicking a bone marrow aspirate. Basophilia is a general clue to the presence of a myeloproliferative neoplasm (MPN).
transfusion-transmitted bacterial infection.
Clinical criteria for a possible septic transfusion reaction include any of the following within 5 hours of completion of a transfusion: temperature greater than 39.0 °C (102.2 °F) or temperature two degrees higher than pretransfusion, rigors, pulse rate greater than 120/min or more than 40/min higher than pretransfusion, or a decrease or increase in blood pressure of greater than 30 mm Hg.
Transfusion should be stopped immediately and intravenous fluids and antibiotics should be given to patients experiencing transfusion-transmitted bacterial infection.
Patients with sickle cell disease undergoing low- to moderate-risk surgery
should receive erythrocyte transfusion, which has been shown to be equivalent to exchange transfusion, targeting a hemoglobin level of 10 g/dL (100 g/L) before the procedure to avoid complications.
The “4T score”
degree of thrombocytopenia, timing of the decrease in platelet count, presence of potential sequelae of HIT (such as thrombosis), and whether another potential cause for thrombocytopenia exists
HIT develops 5 to 10 days after exposure to heparin, with a decrease in platelet counts of 50% or more and, in a subset of patients, paradoxical arterial or venous thrombotic events despite the presence of thrombocytopenia.
Treat a patient with venous thromboembolism who wishes to breastfeed.
Warfarin and low-molecular-weight heparin are considered safe for use by women requiring anticoagulant therapy who wish to breastfeed.
alpha thalasemia
α-thalassemia shows a normal pattern and β-thalassemia typically has a slightly increased hemoglobin A2 band. α-Thalassemia trait (or α-thalassemia minor, double gene deletion -α/-α or –/αα) is associated with mild anemia, microcytosis, hypochromia, target cells on the peripheral blood smear, and, in adults, normal hemoglobin electrophoresis results. The (-α/-α) variant is often mistaken for iron deficiency.
The red cell distribution width (RDW) is also useful in distinguishing between thalassemia and iron deficiency, because the RDW is often elevated in iron deficiency but normal in thalassemia. No treatment or monitoring is necessary for α-thalassemia trait.
Glucose-6-phosphate dehydrogenase deficiency
pisodic hemolysis in response to oxidant stressors (for example, infections or drugs such as dapsone, trimethoprim-sulfamethoxazole, and nitrofurantoin)
x linked
uring an acute hemolytic episode, bite cells may be seen on the peripheral blood smear, as are apparent in this patient’s peripheral blood smear.
Felty syndrome
characterized by rheumatoid arthritis, splenomegaly, and neutropenia.
The unusual cell seen on the peripheral blood smear is a large granular lymphocyte (LGL). LGLs may be seen in up to 40% of patients with Felty syndrome; they may also be associated with other collagen vascular diseases and autoimmune neutropenia.
