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HEMATOLOGY

Hemostatis
-PT and PTT (know factors)
-factor 7 has the shortest half life and therefore PT will show up first as being abnormal
-use PT to monitor Coumadin
-use PTT to monitor Heparin
-all factors are made in the liver except VIII (endothelium)
Platelet problem
-petechiae, purpura, ecchymosis
-test by using platelets and BT
Coagulation
-deep tissue bleeding, hemarthroses
-test by using the PT and PTT

PLATELET DISORDERS
Problems with the numbers
-normal platelet count is 250,000
-bleeding usually with platelets <20,000
-spontaneous bleeding with platelets <10,000 (intracranial bleeding)
-scarcity of platelets on a blood smear!
-marrow failure d/t leukemia (leukoeryroblastemia & myleopthysis),
aplastic anemia, myelofibrosis (myelodysplastic syndromes)
chemotherapy syndromes and ethanol, B12 and folate deficiency (DNA)
Problems with Splenic Sequestration
-usually counts of 40-100,000 (no bleeding) – hypersplensim and splenomegaly
-low WBC
-splenectomy not usually necessary
Problems with destruction
ITP TTP HUS
Fine except for petechiae and purpura HUS + FEVER and CNS Low platelets +
Labs are all normal except for platelets Hemolysis d/t verotoxin (O157:H7)+
BM shows increased platelets Thromobocytopenia Uremia
Associated with MAHA (micro-angiopathic hemolytic anemia)
-mono, SLE, Hodgkin’s, and CLL Seizures, coma Associated with bloody diarrhea
-also HIV, pregnancy, quinidine, sulfa, gold Arteriolar plugging in the kidney
-SLE drugs (hydralizine, procainamide) histone Fever No fever or neurological signs
Treatment Treatment
-IVIg steroids, vincristine, splenectomy -plasma exchange
look for accessory spleens,
never give platelets
Problems with function (abnormal bleeding times) – BT
1) Aspirin
2) NSAIDS
3) VWD
4) Uremia (kidney failure)

COAGULATION DISORDERS
HEMOPHILIA A (factor VIII:c) VWF (factor VIII:ag)
-X-linked usually males -VWF stabilizes factor VIII, aggregation, adhesion
-soft tissue and point bleedings, CNS bleedings with minor trauma -mucous membrane bleeding, prolonged bleeding from gums
-spontaneous hematuria  ureteral colic (blood clots in the ureter) -menorrhagia
-PTT and VIII:c but normal VWF -PTT, BT, VII, VWF, abnormal aggregation with riscocetin
-Treatment = VIII replacement (need to measure) -Treatment
watch out for HCV and HIV (common but less now d/t expensive form) cryoPPT with VIII and VWF
watch out for antibodies to the factor (the factor will not rise on trans. DDAVP
It’s OK to have Sx – just keep track of the levels Estrogens and OCP increase VWF
Acquired Coagulation Disorders
Vit K Liver Disease DIC Lupus Anticoag.
2,7,9,10,S,C -everything low except for factor -wide spread activation -doesn’t have to be SLE
-need to eat but also bacteria makes VIII -depletion of the factors -many patients don have SLE
-poor intake, fat malabsorption, -PT is the first sign -fibrinolysis  FSP -PTT in vitro
-antibiotics can kill bacteria PT, PTT, BT =actually hypercoaguable
-Fibrinogen -seen in miscarriages in 2nd tri
-MAHA  schistocytes
CAUSES:
-sepsis, dead fetus, eclampsia
-TTP, HUS, MAHA, M3 AML
-Tx = heparin only for M3 AML

ANEMIAS
Hypochromic anemias
Fe Deficiency Sideroblastic Anemia of Chronic Disease
CAUSES -defect in heme synthesis -can’t use the Fe
-imbalance between diet and needs -excess Fe in the mitochondria -diminished response to EP from the kidney
-usually due to menstrual or GI bleed -more absorption of Fe in the proximal gut -Fe, TIBC, ↑ferritin, MCV, retics
-achlorhydria (reduced absorption) hemochromatosis results -don’t give EP or Fe but treat underlying
seen in pernicious anemia or omeprazole -seen with INH, ethanol, PLP def, disease
-hospital phlebotomy -Tx = PLP (vit B6)
LAB FINDINGS
-first becomes microcytic then hypochromic
-RDW, MCV, ferritin but if chronic disease
-% sat but TIBC
-gold standard is BM with iron stores
Prussian Blue Stain
TREATMENT is with FeSO4
-reticulocytes in 1 week
-Hgb in 3 weeks
-Fe often causes constipation and black stools
also peptobismol turns your stool black
-Prox  distil = Fe++, Ca++, Folate, Vit B12

Macrocytic anemias
Three different mechanisms
1) Accelerated erythropoesis (reticulocytes make the MCV bigger)
2) Increased membrane size (liver disease and large target cells)
3) Defective DNA synthesis (folate or vit B12 deficiency) – megaloblastic (pancytoplastic) anemia

Megaloblastic Anemia In vit B12 you see in addition

-megaloblastic anemias -neurological symmetric myelopathy and neuropathy
-RBCs are large and oval -early paresthesias, late ataxia
-hypersegmented polys (5 or 6 lobes) -cerebral and psychiatric manifestations (don’t T x with folate)
-pancytopenia (affects all of your cells)
Vit B12 deficiency Folate deficiency
Vit b12  binds factor R in saliva  IF made in stomach  pancreatic -Common in alcoholics (dietary deficiency rare)
enzyme cleaves R factor in intestines allowing IF to bind -celiac sprue
Bacteria also consume B12 so that may be a cause of deficiency -impaired folate metabolism d/t drugs, ETOH, methotrexate,
Absorption occurs in the terminal ileum pyrimethamine, septra, sulfasalazine, phenobarbital, and phynetoin
SCHILLING TEST -also caused by increased demand d/t pregnancy
IF CORRECTS WITH: THEN THE DEFECT IS:
IF pernicious anemia or gastrectomy
Pancreatic enzymes pancreatic insufficiency
Antibiotics bacterial overgrowth or blind loop
Diverticulitis Make sure that you don’t get in the “folate trap” by treating a vit b12
PERNICIOUS ANEMIA deficiency with only folate because you’ll correct the anemia but miss the
-most common cause of vit B12 deficiency anemia neurological symptoms.
-severe atrophic gastritis
-antibodies to parietal cells or IF
-associated with Hashimoto’s Graves, DM, Addison’s and vitiligo
-Thymomas
-increased risk of gastric cancer & carcinoid d/t low acid and high gastrin
Hemolytic anemias
RBC membrane defects Enzyme defects (G6PD def) Hemolytic Anemias
HSS (hereditary spherocytosis) -10% of AA males WARM
-mild hemolytic anemia, jaundiced -sulfa, quinine, furantoin, sepsis, hepatitis -positive direct Coombs test
-spelomegaly and bilirubin gallstones -Heinz bodies are trapped in the spleen -IgG or C’ @ 31.1 C
-osmotic fragility -Dx = quantifiying the G6PD activity -SLE, lymphoma, CLL or drugs
-Tx = splenectomy may be normal after hemolysis episode COLD
Acanthocytosis -cold agglutinins @ 4 C
-spur cells with liver dis or abetalipoproteinemia -IgM
-steatorrhea or retinitis pigmentosa -mycoplasma or mono
Stomatocytosis DRUG induced
-RBCs with a slit – seen in ETHANOL ABUSE -Hapten – penicillin (binds membrane)
-reversible -Bystander – quinidine, sulfa, phenothiazines
-Alpha-methydopa – (modifies membrane)

Hemoglobinopathies
Sickle Cell Disease Thalassemias
-usually due to intravascular sickeling, vascular thrombosis, infection -most common is thalassemia minor
-leg ulcers, chronic hematuria, renal papillary necrosis beta
-functional asplenia -normal life expectancy in Mediterranean, Southern Europe, Africa
-priapism  impotence -high HgbA2, low MCV, high RBC, mild reticocytosis
-pigmented gallstones (billirubin Ca++  radio opaque stones)
cholesterol stones are radio lucent
-bone infarcts  aseptic necrosis of femoral heads
-osteomyelitis  salmonella common (need bone scan)
-pulmonary infarct  cor pulmonale (right heart failure)
-drug addictions because most need to be put on narcotics
ACUTE SICKLE CRISIS
-acute pain and fever (chest syndrome) – give fluids not diuretics
-abdominal pain mimics the acute abdomen
along with DM and also prone to cholecystitis
-need to R/O infection while treating symptomatically
-if infected with B19  aplastic crisis
monitor reticulocyte count and may need RBC transfusion

HEMATOLIGIC MALIGNANCIES
Non Hodgkin’s Lymphoma Hodgkin’s Lymphoma
-Grading is the primary diagnosis and prognosis -B-symptoms = fever, night sweats, weight loss
-low grade  slow grower but no cure or can be asymptomatic (A)
-high grade  fast grower but cure -pain in lymph nodes after ETOH ingestion
-Pel Ebstein fever
Lymphoblastic lymphoma high fever for 2 weeks at a time at night separated by no fever
-meningeal and testicular involvement STAGING (MORE IMPORTANT THAN GRADE)
-most are T-cell and resemble TALL -1 = single node or local site
Adult T-cell lymphoma -2 = more than one node on the same side of the diaphragm
-40,000 WBC -3 = involvement on both sides of the diaphragm
-HTLV-1 (HTLV-2 is for Hairy cell and HTLV-3 is really HIV) -4 = diffuse
-hypercalcemia Dx = RS cells in the lymph nodes
-lytic bone lesions PATHOLOGIC TYPES (GRADE)
-skin infiltration -lymphocyte depletion (worst)
-usually seen in Caribbean and Japan -mixed cellularity
Small cell non-cleaved - Burkitt’s -lymphocyte predominance
-common in Eastern Africa -nodular sclerosis (BEST)
-extranodal involvement WORK-UP
-EBV infection with c-myc t(8,14) -check history for B-symptoms (worse prognosis)
-PDX lymph nodes, liver, spleen, bone tenderness
-LABS – CBC, LFTs, renal failure, TFTs, BM biopsy
-IMAGING – CXR, abdominal CT, lymphangiography (shows size of
lymphs in the abdomen), gallium scan (malignant nodes light up),
exploratory laparotomy (if you’re not sure of spleen involvement and you
need the correct stage)
TREATMENT
I and II  radiation only (may consider chemo if II with b-symptoms)
III and IV  radiation and chemotherapy (MOPP and ABVD)
ACUTE LEUKEMIAS
-uncontrolled proliferation of a malignant clone of hematopoietic cells
-don’t respond to normal regulatory growth factors
-the abnormal clone may suppress the growth and differentiation of normal hematopoietic cells
-problems d/t
1) anemia
2) low platelets
3) low WBC
-Therapy for treatment for ACUTE LEUKEMIAS
Induction Prophylaxis Consolidation Maintenance Relapse
-need complete remission Intrathecal Methotrexate Induction drugs needed to Vincristine, prednisone, Reinduction followed by
-vincristine keep consolidation during methotrexate, 6-MP BM transplant
-prednisone remission
-Doxirubricin

ALL AML
-fatigue, pallor, bruising, petechiae, bleeding, fevers, inf. -increases with age
-bone pain d/t expanding bone marrow mass -Associated with Sweet’s Disease
-ICP d/t leukemic infiltration of the meninges (BAD) -can occur after chemotherapy or myelodysplastic syn
-diffuse lymphadenopathy and hepatosplenomegaly -myeloperoxidase +
LAB VALUES -M3 – acute promyelocytic leukemia
-90% have WBC DIC treated with heparin
-hypocellular marrow with lymphoblasts t(15,17) associated with M3
-normal cells greatly reduced chemo with all trans retinoic acid (vit A)
CELL MARKERS -M5 – acute monocytic leukemia
-most are BALL and express CALLA and TdT skin or gum infiltration with leukemic cells
-TALL is the worst prognosis
CLL CML
-hypogammaglobulinemia -entire spectrum of PMNs from blasts to mature
-STAGES -peripheral smear looks like a BM aspirate
0 = lymphocytosis -Philadelphia Chromosome t(9,22) c-abl
1 = lymphocytosis + big nodes -Low Alkaline Phosphatase
2 = lymphocytosis + big spleen or liver -gradual increase in WBC  massive splenomegaly
3 = lymphocytosis + anemia -terminal phase is blast crisis (survival 6 months)
4 = lymphocytosis + low platelets (bleeding is worse) -Tx = allogeneic hematopoietic cell transplantation (HCT)
-usually 10-15 years survival unless late  2-4 years (for potential cure)
-rarely T-cell (worse) tyrosine kinase inhibitors (TKIs) (for disease control
-death usually due to infection without cure)
Tx = Early stages – not necessary
Late stages – chlorambucil and prednisone
If just spleens or lymph nodes  radiate
If very high WBC  leukopharesis (hyperviscosity)
Hairy cell leukemia
-B-cells with hairy cell projections
-can have huge spleens (just like CML)
-usually slow progression
-Tartrate Resistant Acid Phosphatase
Tx = pentostatin, interferon, and cladribine
Chronic Myeloproliferative Disorders
Polycythemia vera
-uncontrolled proliferation of red blood cells precursors
(Secondary polycythemia)
-increase in RBCs d/t hypoxemia or other stimulus
-itching
-usually 50-70 y/o, hyperviscosity or thrombotic tendencies
-hepatosplenomegaly is very common
-Dx = must R/O hypoxemia, will have high RBC and WBC, elevated B12 (decreased in 2nd poly)

PLASMA CELL DISORDERS

Multiple Myeloma
-monoclonal cells produce M-protein (heavy and light chain)
-most common is G and A
-light chain is 
-late age of onset of 70 years old
-suppression of normal plasma cells  fewer normal immunoglobulins (more infections)
HI and SP
-bone destruction common due to OAF, IL-1, THF
-lytic lesions common in skull, lower back, pelvis, rib cage (also presents as osteopenia)
-hypercalcemia especially with bone destruction
-renal insufficiency (amyloid or obstructed ureters)
-hyperviscosity syndrome (confusion, visual impairment, purpura)
Diagnosis
-serum and urine SPEP (electrophoresis) and IPEP (to figure out the type of Ig)
-skeletal X-ray survey
-bone marrow has >20% plasma cells
Prognosis
-2 microglobulin is a marker of total myeloma
-low 2 and younger patients have best prognosis
-worst prognosis = older, high 2, high LDH, low platelets
Treatment
-if symptomatic  melphalan and prednisone
-bone pain management  effective chemotherapy
 radiation if sharply localized pain or pending fracture
 mobilize patient
 positive Ca++ balance
 biphosphonates to inhibit bone resorption
Plasmacytoma
-localized collection of monoclonal plasma cells (usually younger patients)
-can occur in bone or extramedullary (usually in upper airways) – don’t cause bone destruction
or cause renal failure
-after surgical excision, monoclonal protein should disappear from blood and urine

Heavy-chain disease
--component of the immunoglobulin heavy chain
-infiltrates small bowel and causes malabsorption

Waldenstrom’s macroglobulinemia
-older men with IgM (big SPEP spike IgM)
-hyperviscosity occurs which responds to plasmapheresis
-binds to platelets and clotting factors  epistaxis, gingival bleeding
-binds to peripheral nerves  peripheral neuropathy

Primary amyloidosis
-neoplasm – monoclonal
-light-chain immunoglobulin
-deposits in tongue  macroglossia (difficulty swallowing)
-stain positive with Congo Red
-amyloid is multisystemic; involves heart, intestines(malabsorption), liver, kidney, nervous system

MGUS
-persistent monoclonal gammopathy
-low serum levels of the M-protein
-spike on SPEP (may not be a malignancy)
-bone marrow plasma cells <10%
-asymptomatic
-1/3 of patients progress to multiple mywloma within 10 years

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