Part 20. Diseases of the Blood Flashcards
Except Anemias
1
Q
Pancytopenia with hypocellular BM is seen in what conditions?
give 3
A
- inherited bone marrow failure syndromes (IBMFSs) with pancytopenia
- acquired aplastic anemia of varied etiologies, and
- the hypoplastic variant of myelodysplastic syndrome (MDS)
2
Q
Pancytopenia with cellular BM is seen with?
give at least 5
A
- primary bone marrow disease (e.g., acute leukemia, myelodysplasia)
- secondary to autoimmune disorders (e.g., autoimmune lymphoproliferative syndrome, systemic lupus erythematosus)
- vitamin B12 or folate deficiency,
- storage diseases (e.g., Gaucher, Niemann-Pick)
- overwhelming infection
- sarcoidosis, and
- hypersplenism
3
Q
Pancytopenia with BM infiltration can be seen in?
A
- metastatic solid tumors
- myelofibrosis
- hemophagocytic lymphohistiocytosis
- osteopetrosis
4
Q
What condition is considered the most common of the inherited pancytopenias?
A
Fanconi Anemia
5
Q
Pattern of inheritance of Fanconi Anemia
A
autosomal recessive
one uncommon form is X-linked recessive
6
Q
True or False
Patients with Fanconi Anemia have a predisposition to malignancy, including myelodysplasia (MDS), acute myeloid leukemia (AML), and epithelial cancers.
A
True
7
Q
The classic Fanconi Anemia phenotype includes the triad of?
A
- Bone Marrow Failure
- Congenital anomalies
- Elevated chromosomal fragility
8
Q
The most common congenital anomalies in Fanconi anemia involves which system?
A
skeletal and include absence of radii and/or thumbs that are hypoplastic, supernumerary, bifid, or absent.
9
Q
Characteristic facial dysmorphisms found in many patients with Fanconi anemia.
A
microcephaly, small eyes, epicanthal folds, and abnormal shape, size, or positioning of the ears
10
Q
The most frequent solid tumors assoc with Fanconi Anemia are
A
- squamous cell carcinomas (SCCs) of the head and neck (600-fold higher risk than the general population)
- and carcinoma of the upper esophagus (2000-fold higher risk), the vulva (3000-fold higher risk), and/or anus, cervix, and lower esophagus.
11
Q
Diagnosis of Fanconi Anemia can be confirmed with?
A
Lymphocyte chromosomal breakage study done with and without the addition of cross-linking agents such as DEB (diepoxybutane) and MMC (mitomycin C), the latter will test for chromosomal fragility
12
Q
The only curative therapy for the hematologic abnormalities observed in FA patients
A
HSCT
13
Q
What therapy is not curative for FA but is used rather as a bridge while waiting for a suitable donor?
A
Androgen therapy.
Oral oxymetholone and danazol are the 2 most commonly used androgenic drugs.
Side effects of androgens include masculinization, increased linear growth, increased mood swings or aggressiveness, elevated hepatic enzymes, cholestasis, peliosis hepatis (blood-filled hepatic sinusoids), and liver tumors
14
Q
What is the underlying defect in Schwachman-Diamond Syndrome?
A
Ribosomopathy, defect in ribosome assembly
15
Q
Pattern of inheritance of SDS?
A
Autosomal recessive
16
Q
What are the defining features of SDS?
A
Hematologic abnormalities (most common neutropenia) and exocrine pancreatic insufficiency (causing fat malabsorption)
17
Q
Tests that can be used to determine pancreatic insufficiency in SDS?
A
Serum trypsinogen (low), pancreatic isomylase (low),
fecal elastase (low)
18
Q
What are similarities and distinguishing features of SDS from FA?
A
SDS shares some manifestations with Fanconi anemia, such as bone marrow dysfunction and growth failure, but patients with SDS are readily distinguished because of pancreatic insufficiency with fat malabsorption, fatty changes within the pancreatic body visualized by imaging, characteristic skeletal abnormalities not seen in FA, and a normal chromosomal breakage study with DEB and MMC.
19
Q
Treatment for SDS
A
Pancreatic insufficiency : oral pancreatic enzymes and fat soluble vitamins
SEvere neutropenia : GCSF
Severe BM failure : allogenic HSCT
20
Q
The diagnostic triad of mucocutaneous features of dyskeratosis congenita.
A
- dysplastic nails
- lacy reticular pigmentation of the upper chest &/or neck
- oral leukoplakia
However, the triad is not present in all individuals. If it occurs, skin and nail findings usually become apparent in the 1st 10 yr of life, whereas oral leukoplakia may be noticed later.
21
Q
Etiology of Dyskeratosis congenita
A
multisystem telomere disorder
22
Q
Clinical criteria for classic DC?
A
Presence of at least 2 of the 4 major features—abnormal skin pigmentation, nail dystrophy, leukoplakia, and bone marrow failure—and 2 or more of the other somatic features known to occur in DC.
In classic disease, skin pigmentation and nail changes typically appear first, usually in the 1st decade of life. Bone marrow failure usually develops within the 1st 2 decades, with 80% of patients developing bone marrow failure by age 30 yr and almost 90% of patients having bone marrow failure at some point in their life.
23
Q
The initial hematologic change in DC?
A
The initial hematologic change in DC is usually thrombocytopenia, anemia, or both, followed by pancytopenia and aplastic anemia. The red cells are often macrocytic, and the fetal hemoglobin is elevated. Initial bone marrow specimens may be normocellular or hypercellular, but with time, a symmetric depletion of all hematopoietic lineages ensues.
24
Q
Distinguishing features of DC against FA.
A
nail dystrophy, leukoplakia, tooth abnormalities, hyperhidrosis of the palms and soles, and hair loss.
25
This condition typically manifests in infancy as isolated thrombocy- topenia caused by reduction or absence of bone marrow megakaryocytes with initial preservation of granulopoietic and erythroid lineages.
Congenital Amegakaryocytic Thrombocytopenia (CAMT)
Autosomal recessive
26
Most common anomalies associated with CAMT
| Body system
Neurologic - developmental delay is a prominent feature
Cardiac - CHDs
27
Hallmark of aplastic anemia
peripheral pancytopenia, coupled with hypoplastic or aplastic bone marrow
28
The presence of ____ is suggestive of congenital pancytopenia but is not diagnostic
Fetal hemoglobin
29
For patients with acquired aplastic anemia without a sibling donor, the major form of therapy is?
immunosuppression with horse antithymocyte globulin (ATG) and cyclosporine
(median time to response is 6mos)
30
These hematologic disorders in Down Syndrome patients does not require aggressive therapeutic approach as these diseases in this specific population are very responsive to conventional chemotherapy
Myelodysplastic syndrome (MDS) and Acute myelocytic Leukemia (AML)
31
In the preoperative period, Hb level ____ is an acceptable level
>= 7g/dL
32
Blood transfusion may be indicated in the treatment of hemorrhage if estimated blood loss is ____ % of the circulating blood volume and the pt's condition is unstable despite initial IV fluids
> 25%
33
Preoperative autologous blood collections from the patient occur up to ____wk before the surgery
6
34
For children and adolescents with overt bleeding, therapeutic PLT transfusions should be given when the blood PLT count falls below ____ × 10^9/L and repeated as needed to maintain the PLT count at this level during bleeding and for 48 hr after bleeding ceases to allow the clot to “stabilize.”
50
35
For a major invasive procedure (e.g., surgical), the PLT count should be maintained >____ × 10^9/L until any bleeding that occurs ceases and the patient is stable.
50
36
The risk of spontaneous bleeding increases when blood PLT levels fall to < ____ × 10^9/L, particularly when hemorrhagic risk factors are present.
20
37
When managing patients with PLT dysfunction, it is important to remember that an abnormal test result with a modern PLT function device or, historically, a ____ more than twice the upper limit of normal provides diagnostic evidence of PLT dysfunction.
Bleeding time
38
Thrombopoietin (TPO) levels are ____ in healthy neonates than in older individuals
| higher or lower?
higher
39
PLT counts < ____ × 109/L pose significant clinical risks for premature neonates.
100
40
Dosing of PLT concentrates or pheresed PLTs for children weighing up to 30kg?
5-10 mL/kg
41
PLT transfusion rate
may be transfused as rapidly as the patient’s overall condition permits, certainly within 2 hr, but not longer than 4 hr.
42
For those infants weighing < 1500 g at birth, what is recommended to prevent transfusion-associated GVHD?
Irradiation
43
When is granulocyte transfusion (GTX) recommended?
only when serious infections are clearly unresponsive to antimicrobial drugs
44
Transfusion of plasma is efficacious for the treatment of deficiencies in clotting factors ?
II, V, X, XI
45
Cryoprecipitate can be used to treat deficiency of ?
Factor XIII and fibrinogen
46
What is an important indication for plasma transfusion?
For rapid reversal of the effects of warfarin in patients who are actively bleeding or who require emergency surgery (in whom functional deficiencies of vitamin K–dependent factors II, VII, IX, and X cannot be rapidly reversed by vitamin K administration)
47
Indications for plasma transfusion in neonates
| 4
(1) reconstitution of red blood cell (RBC) concentrates to simulate whole blood for use in massive transfusions (exchange transfusion, cardiac bypass surgery, and extracorporeal membrane oxygenation),
(2) hemorrhage secondary to vitamin K deficiency
(3) disseminated intravascular coagulation with bleeding, and
(4) bleeding in congenital coagulation factor deficiency when more specific treatment is either unavailable or inappropriate
48
What is the most efficacious method currently available to prevent transfusion-transmitted CMV?
perform leukoreduction in the blood center/bank without regard for the CMV antibody status of the donor
49
How may the risk of transfusion-related acute lung injury (TRALI) be reduced?
by avoiding transfusion of plasma or platelets from female donors, who were possibly alloimmunized to leukocyte antigens during pregnancy, or by selecting donors (e.g., males) who are likely to be negative for human leukocyte antigen (HLA) antibodies.
50
# True or False
Leukocyte reduction can be substituted for irradiation to prevent GVHD.
False. It cannot, however, pathogen-reduction technologies have been demonstrated to be efficacious
51
Main components of the hemostatic process
| 5
1. vessel walls
2. platelets
3. coagulation proteins
4. anticoagulant proteins
5. fibrinolytic system
52
53
54
55
Rate-limiting steps in the clotting process
those involving the cofactors factor VIII (X-ase complex) and factor V (pro- thrombinase complex)
56
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Four clinically important, naturally occurring anticoagulants that regulate the extension of the clotting process:
1. Antithrombin III (ATIII)
2. Protein C
3. Protein S
4. Tissue Factor Pathway inhibitor )TFPI)
57
The 2 most common severe bleeding disorders
Factor VIII and Factor IX deficiencies
(Hemophilia A and B)
58
Patients with clotting factor deficiency usually have bleeding where?
deep bleeding into muscles and joints, with much more extensive ecchymoses and hematoma formation
59
Mucocutaneous bleeding may be a sign of?
defects in platelet-blood vessel wall interaction (vWD or platelet function defects)
60
# True or False
Thrombocytosis in children is usually reactive and is not associated with bleeding or thrombotic complications.
True
61
This measures the activation of clotting by tissue factor (thromboplastin) in the presence of calcium.
Prothrombin time (PT)
62
This test measures the initiation of clotting at the level of factor XII through sequential steps to the final clot end-point.
Partial thromboplastin time (PTT)
63
The PTT can be prolonged by deficiencies of?
factor XII, prekallikrein, and high-molecular-weight kininogen, yet these deficiencies do not result in bleeding
64
This measures the final step in the clotting cascade, in which fibrinogen is converted to fibrin
Thrombin time (TT)
65
PT tests for which coagulation factors?
II, V, VII, X (extrinsic pathway)
66
PTT tests for coagulation factors?
VIII, IX, XI, XII (intrinsic pathway)
67
Prolongation of TT occurs with what conditions?
reduced fibrinogen levels (hypofibrinogenemia or afibrinogenemia), with dysfunctional fibrinogen (dysfibrinogenemia), or in the presence of substances that interfere with fibrin polymerization, such as heparin and fibrin split products
68
When a qualitative platelet function defect is suspected, what is usually ordered?
platelet aggregation testing
69
Hallmark of hemophilic bleeding.
Hemarthrosis
70
The earliest joint hemorrhages in hemophilic patients appear most often where?
ankle
71
A pt with hemophilia may lose large volumes of blood into which muscle verging on hypovolemic shock, with only a vague area of referred pain in the groin?
Iliopsoas
72
What are the classifications of Hemophilia according to severity and briefly describe each.
__Severe__: having < 1% activity of the specific clotting factor, and bleeding is often spontaneous
__Moderate__: factor levels of 1–5% and usually require mild trauma to induce bleeding.
__Mild__: levels >5%, may go many years before the condition is diagnosed, and frequently require significant trauma to cause bleeding.
73
The hemostatic level for factor VIII is > ____, and for factor IX is > ____.
30-40%
25-30%
74
Mode of inheritance of hemophilia A
X-linked recessive
75
Mode of inheritance of Hemophilia B
X-linked recessive
76
Mode of inheritance Hemophilia C
Autosomal recessive
77
When mild to moderate bleeding occurs, values of the deficient factor must be raised to hemostatic levels, usually in the range of ?
35 - 50%
78
In cases of major hemorrhages (in hemophiliacs), values of the deficient factor must be raised to ?
levels of 100% activity
79
Dose of rFVIII (IU) =
% Desired (rise in FVIII) × Body weight (kg) × 0.5
80
Dose of rFIX (IU) =
% Desired (rise in plasma FIX) ×Body weight(kg)×1.3
81
What drug can be used in mild factor VIII hemophilia?
Desmopressin acetate
82
In patients with severe hemophilia, when is prophylaxis initiated?
with the 1st or 2nd joint hemorrhage.
83
What is the major long-term disability associated with hemophilia?
Chronic Arthropathy
84
This is an immune response to infusion of clotting factors in hemophiliacs wherein antibodies directed against factor VIII or factor IX that block the clotting activity.
Inhibitor Formation
85
The bispecific, humanized monoclonal antibody can bridge activated factor IX and factor X, thus restoring functional activated factor VIII activity in patients with hemophilia (with or without factor VIII inhibitors)
emicizumab
86
What clotting factor is deficient in Hemophilia C?
Factor XI
87
# True or False
The bleeding associated with factor XI deficiency is correlated with the amount of factor XI
False
88
89
90
What is a condition/situation in which PTT is extremely prolonged with no evidence of clinical bleeding?
Deficiency of the “contact factors”—factor XII, prekallikrein, and high- molecular-weight kininogen
| they do not need treatment, even for major surgery.
91
This is prolonged only by reduced or dysfunctional fibrinogen and fibrin split products.
Reptilase time
92
Clinical symptoms of this factor deficiency include mild bruising, delayed separation of the umbilical stump beyond 4 wk in neonates, poor wound healing, and recurrent spontaneous abortions in women.
Factor XIII
It is responsible for the cross linking of fibrin to stabilize the fibrin clot, symptoms of delayed hemorrhage are secondary to instability of the clot. Typically, patients have trauma 1 day and then have a bruise or hematoma the next day.
93
What is the most common inherited bleeding disorder?
von Willebrand Disease
94
Patients with type 1 VWD have a vWF:Ag levels of < ____?
30 IU/dL
95
Type 1C vWD is a subtype of type 1 vWD resulting from increased clearance of their VWF. Why is diagnosis of this subtype important?
Because treatment of these patients with desmopressin is likely to be ineffective, necessitating administration of VWF-containing products.
96
Lower VWF levels seen in people with this blood type.
O
97
What are factors that can increase vWF levels? decrease vWF levels?
* __Increase__ : stress, exercise, pregnancy
* __Decrease__ : hypothyroidism, certain medications like valproic acid
98
In addition to mucosal bleeding, patients with this type of VWD may experience joint bleeds or central nervous system hemorrhage.
Type 3 VWD - most severe form, vWF protein is completely absent and these patients typically have very low FVIII (< 10 IU/dL)
99
This type of VWD is characterized by a defect in VWF multimerization and decreased VWF activity in terms of platelet binding.
Type 2A VWD
It is the most common of the type 2 variants
100
This type of VWD results from gain-of-function mutations that increase the ability of VWF to bind platelets, leading to increased clearance of both VWF and platelets from circulation and results in the loss of HMW multimers and decreased VWF activity.
Type 2B VWD
101
This occurs when a mutation in platelet GPIb causes spontaneous binding to VWF and also presents with decreased VWF activity, loss of HMW multimers, and thrombocytopenia.
Platelet-type pseudo-VWD
102
This is generally caused by a defect in the ability of VWF to bind platelet GPIb, but this category also includes patients with defects in VWF-collagen interactions.
Type 2M VWD.
Patients have decreased VWF activity but normal (or near-normal) multimer distribution.
103
This is characterized by a defect in the ability of VWF to bind FVIII and may be misdiagnosed as mild hemophilia.
Type 2N VWD.
a high index of suspicion for this diagnosis is required in patients with low FVIII and an absent family history of FVIII deficiency.
104
This test measures the total amount of VWF protein present,
vWF antigen test (vWF:Ag)
105
This test provides a measure of the amount of functional VWF.
vWF activity / ristocetin cofactor activity assay (VWF:RCo)
106
Treatment for type 1 VWF
DDAVP / Desmopressin - induces release of vWF from endothelial cells. Not useful for type 1C vWF.
107
Treatment/s for type 2, 3, and severe type 1 vWD?
vWF concentrates
108
Adjuct treatment/s for vWD with mucosal bleeding
Antifibrinolytics (Aminocaproic acid, tranexamic acid)
109
Adjunct treatment for vWD patients with menorrhagia.
Hormonal therapy
110
What is the most common inherited risk factor for thrombosis?
Factor V Leiden mutation. This mutation causes factor Va to become resistant to inactivation by activated protein C.
111
This rare condition is characterized by rapidly spreading purpuric skin lesions resulting from thromboses of the small dermal vessels, followed by bleeding into the skin.
Purpura fulminans
112
Neonates with homozygous deficiencies of one of these proteins may present with rapidly spreading purpuric skin lesions.
Anticoagulant proteins : AT III, Protein C, or Protein S
113
An infant with purpuric skin lesions of unknown cause should receive initial replacement with ?
Fresh frozen plasma
114
An inborn error of metabolism which is associated with both venous and arterial thromboses in young patients.
Homocystinuria, caused by deficiency of cystathione β-synthase.
115
Increased plasma concentration of this factor is associated with an increased risk of thrombosis
Factor VIII
116
What is the most important risk factor for Venous thromboembolism in pediatric patients?
The presence of a central venous catheter (CVC, peripherally inserted central venous catheter)
117
What are the most common medical conditions associated with TEs?
Cancer, congenital heart disease, and prematurity
118
What is the most common spontaneous VTE in neonates?
Renal vein thrombosis.
Affected infants may present with hematuria, an abdominal mass, and thrombocytopenia
119
What is a fragment produced when fibrin is degraded by plasmin and is a measure of fibrinolysis?
D-dimer, predictive value for DVT is not as well established for children.
120
Over time, an occluded deep vein may cause venous hypertension, resulting in blood flow being directed from the deep system into the superficial veins and potentially producing pain, swelling, edema, discoloration, and ulceration. This clinical picture is known as?
Postthrombotic syndrome (PTS)
121
Initial options for anticoagulation in children
Unfractionated heparin (UFH) or Low molecular weight heparin (LMWH), followed by LMWH or warfarin for outpatient management
122
If the antico- agulant effect of heparin must be reversed immediately, what may be administered to neutralize the heparin?
protamine sulfate
123
This is a prothrombotic, immune-mediated complication in which antibodies develop to a complex of heparin and platelet factor 4.
__Heparin-induced thrombocytopenia (HIT)__
These antibodies result in platelet activation, stimulation of coagulation, thrombocytopenia, and in some cases, life-threatening thrombosis.
124
What is the most frequently used anticoagulant in pediatric patients?
LMWH
125
What test can be used to measure the anticoagulant effect of LMWH?
The several LMWHs available have variable inhibitory effects on thrombin. For this reason, the PTT is not a reliable measure of the anticoagulant effect of LMWH, and the __anti–factor Xa activity__ is used instead.
126
Vitamin K-dependent coagulation factors?
Factors II, VII, IX, X, protein C and S
127
What is used to monitor the anticoagulant effect of warfarin?
PT
128
What is used to monitor the anticoagulant effect of UFH?
PTT
129
What is the MOA of warfarin?
Warfarin is an oral anticoagulant that competitively interferes with vitamin K metabolism, exerting its action by decreasing concentrations of the vitamin K–dependent coagulation factors II, VII, IX, and X, as well as protein C and protein S.
130
What is the INR target range for the treatment of VTE?
2.0 - 3.0
131
What is the primary agent used for thrombolysis in children?
Tissue plasminogen activator (TPA)
Because of the high risk of bleeding, thrombolytic therapy is generally reserved for patients with life- or limb-threatening thrombosis.
132
In the event of serious bleeding, thrombolysis should be stopped and what should be given ?
__cryoprecipitate__ to replace fibrinogen.
133
All clotting factors are produced exclusively in the liver, except?
Factor VIII
134
Treatment of the coagulopathy of liver disease
Vitamin K (PO, IV, SC, but not IM)
FFP
Cryoprecipitate (1unit / 5-10kg BW)
135
What can be used for severe liver disease associated with moderate prolongation of bleeding time that is not corrected by vitamin K or plasma replacement?
__Desmopressin__ (0.3 μg/kg intravenously) is effective in shortening bleeding time and is used effectively to augment hemostasis before liver biopsy.
136
The most common form of antiphospholipid antibodies?
lupus anticoagulant
137
What are the most critical steps in the treatment of DIC?
treat the trigger that caused DIC and restore normal homeostasis by correcting the shock, acidosis, and hypoxia that usually complicate DIC.
138
Platelets circulate with a lifespan of ?
10 - 14 days
139
What is the primary growth factor that controls platelet production?
Thrombopoietin (TPO)
140
What is the most common cause of acute onset of thrombocytopenia in an otherwise well child?
Idiopathic Thrombocytopenic Purpura (ITP)
141
Peak age for ITP?
1 - 4 y/o
142
UK classification of ITP.
1. No symptoms
2. Mild symptoms: bruising and petechiae, occasional minor epistaxis,
very little interference with daily living
3. Moderate symptoms: more severe skin and mucosal lesions, more
troublesome epistaxis and menorrhagia
4. Severe symptoms: bleeding episodes—menorrhagia, epistaxis,
melena—requiring transfusion or hospitalization, symptoms interfering seriously with the quality of life
143
Indications for bone marrow aspiration/biopsy in a patient with thrombocytopenia.
an abnormal WBC count or differential or unexplained anemia, as well as history and physical examination findings suggestive of a bone marrow failure syndrome or malignancy.
144
What is Evans Syndrome?
Autoimmune hemolytic anemia and thrombocytopenia.
It may be idiopathic or an early sign of systemic lupus erythe- matosus, autoimmune lymphoproliferative syndrome or common variable immunodeficiency syndrome
145
What must be considered in young males found to have thrombocytopenia with small platelets, particularly if there is a history of eczema and recurrent infection?
Wiskott-Aldrich Syndrome
146
When is interventional treatment for ITP indicated and what is the treatment of choice?
Treatment with either IVIG or corticosteroids, particularly for children who present with _mucocutaneous bleeding_ (Severe symptoms). As American Society of Hematology guidelines state, “A single dose of IVIG [intravenous immune globulin] (0.8-1.0 g/kg) or a short course of corticosteroids should be used as first-line treatment.”
147
What is the recommended treatment for non-severe ITP?
No therapy other than education and counseling of the family and patient for patients with minimal, mild, and moderate symptoms.
148
When should splenectomy in ITP be considered?
| 2 circumstances
1. the older child (≥4 yr) with severe ITP that has lasted >1 yr (chronic ITP) and whose symptoms are not easily controlled with therapy and
2. when life-threatening hemorrhage (ICH) complicates acute ITP, if the platelet count cannot be corrected rapidly with transfusion of platelets and administration of IVIG and corticosteroids.
149
Definition of chronic ITP?
persistent thrombocytopenia for >12 mo
150
What are some infectious agents associated with development of ITP?
EBV
HIV
H. pylori
151
What medical therapy can be used for chronic ITP?
IVIG, corticosteroids, IV anti-D, or rituximab
152
What are effective agents that act to stimulate thrombopoiesis approved by the U.S. Food and Drug Administration (FDA) to treat adults and children with chronic ITP?
| 2
romiplostim
eltrombopag
153
Some common drugs used in pediatrics that cause thrombocytopenia include?
valproic acid, phenytoin, carbamazepine, sulfonamides, vancomycin, and trimethoprim-sulfamethoxazole
Heparin
154
Recommended treatment for heparin-induced thrombocytopenia includes?
direct thrombin inhibitors such as argatroban or danaparoid and removal of all sources of heparin, including line flushes.
155
The microangiopathic hemolytic anemia is characterized by ?
presence of RBC fragments, including helmet cells, schistocytes, spherocytes, and burr cells.
156
Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy characterized by the pentad of?
1. fever
2. microangiopathic hemolytic anemia
3. thrombocytopenia
4. abnormal renal function, and
5. central nervous system (CNS) changes that is clinically similar to HUS
157
What is the pathophysiology of acquired TTP? Management?
Ab to ADAMTS13
Tx: Plasmapheresis, which should be instituted on the basis of thrombocytopenia and microangiopathic hemolytic anemia even if other symptoms are not yet present
Rituximab, corticosteroids, and splenectomy are reserved for refractory cases
158
What is the pathophysiology of congenital TTP? Management?
Inadequate ADAMTS13 production
Tx: Scheduled plasma infusions
159
The association of a giant hemangioma with localized intravascular coagulation causing thrombocytopenia and hypofibrinogenemia is called?
Kasabach-Merritt Syndrome
160
Arteriovenous malformation within the lesions of Kasabach-Merritt Syndrome can cause?
Heart Failure
161
This usually manifests within the 1st few days to week of life, when the child presents with petechiae and purpura caused by profound thrombocytopenia? Management?
**Congenital amegakaryocytic thrombocytopenia (CAMT)** is caused by a rare defect in hematopoiesis as a result of a mutation in the stem cell TPO receptor (MPL). PE is normal.
**HSCT** is curative.
162
This condition consists of thrombocytopenia (absence or hypoplasia of megakaryocytes) that presents in early infancy with bilateral radial anomalies of variable severity, ranging from mild changes to marked limb shortening
**Thrombocytopenia–absent radius (TAR) syndrome**
Thumbs are present. Intolerance to cow’s milk formula (present in 50%) may complicate management by triggering gastrointestinal bleeding, increased thrombocytopenia, eosinophilia, and a leukemoid reaction.
163
This condition is characterized by thrombocytopenia, with tiny platelets, eczema, and recurrent infection as a consequence of immune deficiency. What is its treatment?
**Wiskott-Aldrich Syndrome**
X-linked dso
BMA: normal number of megakaryocytes, though they may have bizarre morphologic features
Successful **HSCT** cures WAS.
164
What is caused by the development of maternal antibodies against antigens present on fetal platelets that are shared with the father and recognized as foreign by the maternal immune system?
Neonatal alloimmune thrombocytopenic purpura (NATP). Presents in an apparently well child who, within the 1st few days after delivery, has generalized petechiae and purpura.
165
Treatment of NATP?
administration of IVIG prenatally to the mother. Therapy usually begins in the second trimester and is continued throughout the pregnancy. CS delivery
166
What is the treatment for children born to mothers with idiopathic thrombocytopenic purpura (maternal ITP)?
prenatal administration of corticosteroids to the mother and IVIG and sometimes corticosteroids to the infant after delivery.
167
This a severe congenital platelet function disorder, is caused by absence or severe deficiency of the VWF receptor on the platelet membrane. This syndrome is characterized by thrombocytopenia, with giant platelets and greatly prolonged bleeding time (>20 min) or PFA-100 closure time.
Bernard-Soulier syndrome
(Autosomal recessive)
168
This is a congenital disorder associated with severe platelet dysfunction that yields prolonged bleeding time and a normal platelet count. Platelets have normal size and morphologic features on the peripheral blood smear, and closure times for PFA-100 or bleeding time are extremely abnormal.
Glanzmann thrombasthenia
169
# Congenital abnormalities of platelet function
This is a dense granule deficiency caused by defects in lysosomal storage. Affected patients present with oculocutaneous albinism and hemorrhage caused by the platelet defect.
**Hermansky-Pudlak syndrome**
_Chédiak-Higashi syndrome also presents with a dense granule defect, immune dysfunction, and albinism_
170
In all but severe platelet function defects, what may be used for mild to moderate bleeding episodes?
**Desmopressin, 0.3 μg/kg intravenously**
In addition to its effect on stimulating levels of VWF and factor VIII, desmopressin corrects bleeding time and augments hemostasis in many individuals with mild to moderate platelet function defects.
171
A splenic edge felt more than ____ cm below the left costal margin is abnormal.
2
172
Splenic hypofunction is characterized by?
| 3
1. RBC inclusions in peripheral blood smears (Howell-Jolly or Heinz bodies),
2. “pits” on interference microscopy, and
3. poor uptake of technetium or other spleen scans
173
Patients with functional hyposplenism or asplenia are at increased risk for sepsis from?
encapsulated bacteria
174
What infectious agents comprise the top 3 causes of postsplenectomy sepsis?
* Streptococcus pneumoniae (>60% of cases)
* Haemophilus influenzae
* Neisseria meningitidis
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Pneumococcal, meningococcal, and H. influenzae conjugate vaccines given at least ____days before sple- nectomy may reduce postsplenectomy sepsis.
14
176
What prophylaxis should be given until at least 5 yr of age and for at least 2 yr after splenectomy?
Oral penicillin VK
(125 mg twice daily for children < 5 yr old; 250 mg twice daily for children ≥ 5 yr)
177
What may decrease the risk of sepsis in patients whose splenectomy is necessitated by trauma?
surgical splenosis (distributing small pieces of spleen throughout the abdomen)
178
Lymphatic capillaries are present in all organs where blood flow except?
Bone Marrow and Retina
179
This is defined as a multifocal lymphatic malformation that involves soft tissues, abdominal and thoracic viscera, and often bone
Generalized Lymphatic anomaly (GLA)
180
This is characterized by a lymphatic malformation involving single or multiple bones and leading to progressive cortical bone loss.
Gorham-Stout disease (GSD; disappearing bone disease; vanishing bone syndrome)
181
What is the most effective treatment for localized macrocystic lymph malformations?
interventional radiology (IR) with administration of sclerosing agents (OK432, ethanol, bleomycin)
182
This has been shown to be effective when used alone or in combination with IR for complicated or extensive LMs.
Sirolimus
an inhibitor of mammalian target of rapamycin (mTOR)
183
# ```
What is an important cause of lymphedema in Africa, Asia, and Latin America?
Filariasis
Injury to the major lymphatic vessels can cause collection of lymph fluid in the abdomen (chylous ascites) or chest (chylothorax)
184
This is characterized by proliferation of lymphatic endothelial cells and smooth muscle cells in the lungs, leading to airway and lymphatic obstruction, cyst formation, pneumothorax, and respiratory failure.
**Lymphangioleiomyomatosis (LAM)**
occurs in young women and is associated with mutations in the tuberous sclerosis tumor-suppressor gene TSC2 in one third of cases. *Sirolimus* stabilizes lung function, reduces symptoms, and improves life quality. Lung transplantation may be required
185
Most common pathogens in lymphangitis.
Group A streptococci
Staphylococcus aureus
186
When is a lymph node considered enlarged?
When its diameter exceeds 1 cm for cervical and axillary nodes and 1.5 cm for inguinal nodes.
187
This condition presents as firm unilateral posterior cervical adenitis, fever, malaise, elevated erythrocyte sedimentation rate (ESR), atypical lymphocytosis, and leukopenia in children 8-16 yr of age. Nodes range in size from 0.5-6.0 cm, are painful or tender in only 50% of cases.
Kuchiki-Fujimoto Disease (histiocytic necrotizing lymphadenitis).
May also present as fever of unknown origin. It usually resolves within 6 months
188
Patients with this condition present with massive bilateral, painless, mobile cervical adenopathy, along with fever, leukocytosis, high ESR, and polyclonal elevation of immunoglobulin G (hypergammaglobulinemia). Night sweats and weight loss are common.
Sinus Histiocytosis With Massive Lymphadenopathy (Rosai-Dorfman Disease)
benign, usually self-limited. most common sites are the skin, followed by the nasal cavity and sinuses, palate, orbit, bone, and central nervous system
Biopsy (diagnostic): pale histiocytes containing engulfed lymphocytes (emperipolesis), and immunoreactivity to S100 protein in large histiocytes
189
This is an uncommon B-cell lymphoproliferative disorder, usually presents in adolescents or young adults. Enlargement of a single node, most often in the mediastinum or abdomen, is the most common localized presentation.
Castleman Disease (angiofollicular lymph node hyperplasia)
Associated with HHV-8
