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2014 Part XII: Hemostasis and Thrombosis Chapter 117: Thrombocytopenia 2015

HYPERSPLENISM repeated hypothermia, her temperature ranging from 31°C to 34°C dur-
Hypersplenism is distinguished from uncomplicated splenomegaly ing the hospitalizations. On each admission she was thrombocytopenic
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in that pooling is accompanied by increased destruction of platelets, (platelet count 7 to 39 × 10 /L). With no therapy other than rewarming,
391
leukocytes, and erythrocytes in association with increased marrow platelet counts returned to normal in 4 to 10 days. However, a review
precursors of the deficient lines and correction of the cytopenia by of 75 patients admitted with hypothermia (body temperatures 26°C to
391
splenectomy. 374–377 The clinical manifestations, laboratory findings, and 35°C) demonstrated that only three patients were thrombocytopenic.
specific treatment are aimed at the underlying disease (Chap. 55). 378
Imaging studies, such as computed tomographic scans, can be use- THROMBOCYTOPENIA RESULTING
ful for defining the size of the spleen and identifying intrasplenic and
extrasplenic disease. Magnetic resonance imaging defines the blood FROM PLATELET TRAPPING:
flow pattern, which is especially useful for detecting portal or splenic KASABACH-MERRITT SYNDROME
vein thromboses. Cell survival studies using radiolabeled platelets
or red blood cells can be helpful for identifying hypersequestration Kasabach-Merritt syndrome is defined as profound thrombocytopenia
when weighing the need for splenectomy. Most patients with sple- related to platelet trapping within a vascular tumor, either a Kaposi-
nomegaly require therapy for the underlying disease rather than for like hemangioendothelioma or a tufted angioma. 392–395 The syndrome
thrombocytopenia. presents predominantly during infancy, but several adult cases have
been reported. These vascular tumors should be differentiated from
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THROMBOCYTOPENIA ASSOCIATED vascular malformations such as classic benign hemangiomas. Benign
hemangiomas usually are superficial, multiple, not associated with
WITH MASSIVE TRANSFUSION severe thrombocytopenia or DIC (Chap. 130), and usually disappear
during childhood. On the other hand, Kaposi-like hemangioendothe-
Several definitions are used for massive transfusion including transfu- lioma and tufted angioma are low-grade malignant vascular tumors
sion of one blood volume or more than 10 units of packed red blood associated with high morbidity and mortality.
cells (RBCs) in 24 hours and transfusion of more than 4 units of Vascular tumors usually are solitary, can reach 20 cm in diame-
packed RBC over 1 hour. Massive transfusion is required in patients ter, and can be superficial or invade internal organs and the retroperi-
379
with uncontrolled and heavy bleeding. One study of patients requir- toneum. 397–399 Superficial tumors can be recognized by the local red to
ing massive transfusion demonstrated that mild thrombocytopenia purple discoloration of the skin. The histologic types more frequently
(47 to 100 × 10 /L) occurred in all patients after transfusion of 15 red associated with Kasabach-Merritt syndrome are Kaposi-like heman-
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cell units, and more severe thrombocytopenia (25 to 61 × 10 /L) devel- gioendothelioma and tufted angiomas or angioblastomas. 392,393,400,401
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oped after 20 red cell units. 380,381 Several factors contribute to thrombo- Kaposi-like hemangioendothelioma is a locally aggressive, low-grade
cytopenia in massive transfusion, including direct loss of platelets in malignant tumor characterized by infiltrating sheets or lobules of poorly
the exsanguinated blood, dilution of platelets by the transfused RBCs, formed vascular channels and aberrant lymphatic vessels. These tumors
DIC triggered by the disease responsible for the blood loss or that devel- are composed predominantly of plump, round, oval, and/or spindled
ops after trauma, and hypothermia (Chap. 140). Massively transfused endothelial cells with hemosiderin deposits. A tufted angioma is a
392
patients should be treated with fresh-frozen plasma to replace coagu- lesion characterized by the presence of vascular tufts and aggregates
lation factors, and with platelets. The precise ratio of platelets to red of round dilated capillaries, lymphangiomatosis, microthrombi, and
382
cells has not been determined, but studies show that massively trans- hemosiderin deposits. 392,393,402,403 Electron microscopic examination
fused trauma patients demonstrated improved survival with increased shows abnormal endothelial cells with prominent cytoplasmic pro-
transfusion of platelet concentrates. 383,384 jections and wide intercellular gaps, fibrin deposition, and platelet
aggregates within the vessels. The histology of the tumor is useful for
393
differentiating the vascular tumors associated with Kasabach-Merritt
THROMBOCYTOPENIA RESULTING syndrome from benign capillary hemangiomas. 404
FROM HYPOTHERMIA Thrombocytopenia in Kasabach-Merritt syndrome usually is
severe and associated with DIC. Contributing factors include “platelet
405
Transient thrombocytopenia occurs during hypothermia, in both trapping” by abnormally proliferating endothelium within the heman-
animals and humans, when the body temperature falls below 25°C. gioma 406,407 and platelet consumption associated with DIC. Platelet trap-
385
The degree of thrombocytopenia correlates with the degree of the ping has been demonstrated by immunohistochemical staining of the
body temperature drop. Thus, thrombocytopenia is less severe in car- tumors with anti-CD61 antibodies (a marker of platelets and megakary-
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409
111
408
diac surgery patients supported by normothermic systemic perfusion ocytes) and by nuclear studies using Cr-labeled platelets and In
(35°C to 37°C) than in those supported by moderately hypothermic platelet scintigraphy to monitor response to therapy. 410,411 How platelets
systemic perfusion (25°C to 29°C). In this case, the drop in platelet become trapped is not clear. Initial physical entrapment of the platelets
386
count likely results from splenic and hepatic pooling and from cold within twisted abnormal vessels may favor their adhesion to abnormal
387
activation and clearance of platelets. Cold induces clustering of the endothelium, which can lead to platelet activation and aggregation fol-
GPIb complex and rearrangement of its carbohydrate chains, which lowed by activation of the coagulation cascade, fibrin deposition, and
then serve as ligands for the macrophage integrin α β , which mediates formation of microthrombi. Excessive flow and shear rates generated
M 2
their clearance in hepatic macrophages. 388,389 In hypothermic dogs, rad- by arteriovenous shunting within the tumor further increase the level
iolabeled platelets are sequestered in the spleen, liver, and other organs; of platelet activation. Continuous thrombus formation leads to platelet
the platelets return to the circulation when normal body temperature is consumption and activation of the fibrinolytic cascade. Severe throm-
restored. 385,390 The clinical relevance of these observations is illustrated bocytopenia and DIC result.
by reports of patients, often elderly, who are hypothermic after peri- The mainstay of treatment is eradication of the tumor. Several
ods of unconsciousness in inadequately heated rooms. In one report, specific therapeutic modalities have been proposed, but none has
a 69-year-old woman had 13 admissions over an 8-year period with been established as consistently effective. Among the therapies are
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